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Single Dose Drug Interaction Study between Anti-Hypertensive Drug

Valsartan Single Dose Drug Interaction Study between Anti-Hypertensive
Drug Valsartan on Antidiabetic Effect of Su...

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 I nt J Med Res., 2013; 1(7): 356-360
IJMBR
International Journal of Medicobiological
Research
(An International peer review journal)
Journal homepage: www.ijmedres.com; ISSN: 0976-8971

Research article
Single Dose Drug Interaction Study between Anti-Hypertensive Drug Valsartan
on Antidiabetic Effect of Sulfonylureas in Normal a nd Streptozotocin Induced
Diabetic Rats
Chitra. K.S1 , Mohan Kumar. R2, Deepak Kumar Dash 1, Bibekananda Meher3
and Trilochan Satapathy3
1
Department of Pharmacology, Royal College of Pharmacy Science, Raipur – 492 099, Chattisgarh, India. 2Department of Pharmaceutical
Technology, Anna University, Regional Office, Tiruchirappalli - 620 024, Tamil Nadu, India. 3Department of Pharmacology, Columbia
Institute of Pharmacy Sciences, Raipur - 492 001, Chattisgarh, India.

Corresponding author: mkumar.rx@gmail.com

Article information ABSTRACT

Keywords:
Valsartan, Gliclazide,
Hypoglycaemia,
Sulfonylureas, Angeotensin
antagonists
Received on: 15.10.2012
Revised on: 05.12.2012
Accepted on: 01.04.2013
In several incidences revealed that a patient may suffer from more than one disease at a time. In
such conditions more than two drugs are used in the treatment of diseases. Hence, drug - drug
interactions are unpredictable and unavoidable in multi-drug therapy. Diabetes mellitus is such a
metabolic disorder characterized by hyperglycemia and carbohydrate, protein and fat metabolism
disturbances. The aim of this study is to investigate the safety, reliability of Valsartan on the anti
diabetic effect of Gliclazide in normal and diabetic rats. Diabetes was induced by single
intraperitoneal injection of Streptozotocin 50mg/kg in rats. Blood samples were collected from
tail vein at time intervals of 0, 1, 2, 4, 6 and 8h and blood glucose levels were estimated.
Gliclazide produced hypoglycaemia activity in a dose dependent manner in normal and diabetic
condition. From the results it is observed that in the presence of Valsartan, Gliclazide produced no
early onset of action and maintained the anti diabetic activity in diabetes induced group. Hence,
from the study it was concluded that the dose and/or frequency of Gliclazide administration have
little or no effect when both the drugs have been used concomitantly.

1. INTRODUCTION is a group of metabolic diseases characterized by

hyperglycaemia, resulting from defects in insulin secretion,
The drug interaction studies assume much importance insulin action or both. Patients with diabetes mellitus are more
especially for drugs that have narrow margin of safety and susceptible to the vascular complications of hypertension and
where the drugs are used for prolonged period of time. [1] heart failure.[5] Gliclazide is an oral hypoglycaemic agent,
Multidrug therapy leads to the occurrence of drug – drug which is a commonly prescribed drug for the treatment of
interactions during concomitant usage of more than one drug.[2] patients with type II diabetes mellitus who have failed diet and
Drug interactions may have potentially life threatening exercise therapy and it appears to be the most effective insulin
consequences in older adults, who may take several drugs at secretagogue both in first phase insulin secretion and in
once for multiple conditions. The elderly patients are more sustained stimulatory response during long term
susceptible to drug interactions than younger patients because administration,[6] concentration reached after the oral
of age related physiological changes.[3] Drug interactions occur administration of 2.5 mg Gliclazide, and is generally reached
not only with other medications, but also with herbal within 2 to 4 hours.[7] The use of the sulphonylureas drugs,
preparations, dietary supplements, and foods. The interactant angiotensin - converting enzyme inhibitors and angiotensin
may be another drug or may be some other substance in the diet receptor blocker is emphasized in the treatment of diabetic
or in the environment that has contacted the body. Modification complications like diabetic nephropathy. [8] The rennin-
of the action may produce beneficial, planned and expected, or angiotensin - aldosterone system (RAAS) plays an important
adverse unplanned and unexpected effects[4]. Diabetes mellitus role regulating blood volume and systemic vascular resistance,

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 Chitra. K.S, et al.,/Int J Med Res., 2013; 1(7): 356-360 357

which together influence cardiac output and arterial pressure.
The rennin - angiotensin - aldosterone system (RAAS) is a
hormone system that regulates blood pressure and water (fluid)
balance. If the rennin - angiotensin – aldosterone system is too
active, blood pressure will be too high. There are many drugs
that interrupt different steps in this system to lower blood
pressure[9] is a potent, orally active non peptide tetrazole
derivative and selectively inhibits Angiotensin II Receptor type
1 which causes reduction in blood pressure and is used in
treatment of hypertension,[10] appears to be at least as effective
and well tolerated as other commonly used antihypertensive
agents. The drug therefore represents a useful therapeutic
option in the management of patients with hypertension and
will be particularly useful in patients not responding to
intolerant of, anti-hypertensive agents from other drug classes.
is an appropriate choice for first-line treatment of patients with
mild-to-moderate hypertension, and its predictable dose-
responsive efficacy provides a rational basis for titration in
clinical practice. ACE inhibiters are likely to interact with
antidiabetic drugs particularly sulphonylureas, which act
mainly on the cells of pancreas to secrete insulin.[11]
The present study is intended to investigate the possible
drug interaction between Valsartan and Gliclazide, which may Group I: Diabetic controls (STZ 60 mg/kg) given only 0.5%
be useful for the clinically to readjust the dose of Gliclazide, Methyl Cellulose (MC). Group II: Diabetic rats treated with
when it is used along with Valsartan.
2. MATERIALS AND METHODS:
2.1. Animals
Study was conducted on healthy and diabetic r ats (Wistar
strain) of either sex; weighing 150-200 g. All the animals were
housed in polypropylene cages. Animals were housed under
standard conditions (temperature of 28 ± 20 o C and 45 ± 2%
relative humidity) with. Rats were fed with standard animal
pellet diet and water ad libitum. The animals were randomly
distributed into 8 groups of 6 animals each. The study was
conducted with the prior permission from Institutional Animal
Ethics Committee (IAEC) (Approval No. CIP/IEAC/011/12) of
Columbia Institute of Pharmacy Raipur, (C.G.). Studies were
performed in accordance with the CPCSEA guidelines.
2.4. Drug treatment
Gliclazide, Valsartan were suspended separately in 5% (w/v)
methyl cellulose solution and administered as a suspension,
orally. All the animals used in the study were fasted for 18 h
prior to individual drug administration.
2.5. E xperimental Design
The rats were divided into eight groups comprising 6 animals in
each group as follows:
2.6. Normal group
Group I: Control rats given only 0.5% Methyl Cellulose (MC).
Group II: Normal animals treated with Gliclazide
(1.44mg/200g).[14]
Group III: Normal animals treated with Valsartan (30mg/kg).[15]
Group IV: Normal animals treated with both Valsartan and
Gliclazide (combination therapy).
2.7. Diabetic group
Gliclazide (1.44 mg/200 g). Group III: Diabetic rats treated
with Valsartan (30 mg/kg). Group IV: Diabetic rats treated with
both and Gliclazide (combination therapy).
After one week the treatment the blood samples were
withdrawn by tail vein at 0, 2, 4, 6 and 8hr of drug treatment in
fasted animals and blood samples were analyzed for blood
glucose levels by one touch glucometer Accu Check.
2.8. Statistical analysis
The results were expressed as Mean ± SEM. The significance
was determined by applying Two-way ANOVA.
3. RESULTS
3.1. I n Normal Animals

2.2. Drugs The percentage blood glucose levels were calculated at various
time intervals in normal animals. The reduction in the blood
Gliclazide was obtained as gift samples from Aurobindo glucose levels were observed from the 1 st hour to the 8 th hour.
Pharma, Hyderabad. Valsartan was obtained as gift samples The percentage reduction in the blood glucose level in the
from Dr. Reddy’s Laboratories, Hyderabad. Streptozotocin was Gliclazide treated group at the 1st and 2nd h of treatment with
obtained from Hi-media, Mumbai. All the other chemicals used Gliclazide was observed as 34.9% and 27.4%, respectively.
were analytical grade. Then in the 4th h, 6th h and 8th h the blood glucose level found to
be 62.6 %, 67.9% and 68.7% respectively. The pure drug at a
2.3. I nduction of diabetes in rats dose of 1.44 mg/200 g does not produce any anti diabetic effect
at any time point. The percentage reduction in the blood
Diabetes was induced by single intra peritoneal injection of glucose level at 4 th h was found to be 19.5%.The percentage
freshly prepared solution of STZ at the dose of 60mg/kg in reduction in the blood glucose level reaches to 1.9% at the end
0.1M citrate buffer (pH 4.5) to the overnight fasted rats. After 3 of 8h. The blood glucose levels were statistically analyzed and
days of STZ induction, the animals having blood glucose levels were found to be significant in the Gliclazide treated group and
between 250–300 mg/dL were selected for the study. non significant in the Valsartan treated group, when compared
to that of control. When both the drugs administered
concurrently in normal rats as a combination therapy the
percentage reduction in the blood glucose levels of the single

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 Chitra. K.S, et al.,/Int J Med Res., 2013; 1(7): 356-360 358

interaction study was found to be 46.0% and 37.4% during the

2nd and 3rd h and 30.5 %, 19.2% and 10.1 % in the 4th, 6 th and When the two drugs co-administered as a combination
8th hour, respectively. The data’s were shown in table- 1. This therapy in group IV at the 1 st and 2nd h of single dose
combination does no not show any significant effect in the interaction study the percentage changes in blood glucose were
normal animals. found to be 57.3% and 51.1%, respectively in diabetic rats. The
blood glucose levels in the case of single dose interaction was
3.2. I n Diabetic Animals found to be reduced in between 0-8th h, but it was found the
hypoglycemic activity is synergizes when compared to that of
In the case of diabetic rats, Gliclazide was studied at a dose of single Gliclazide treatment. Significant elevations were
1.44 mg/kg, the percent reduction in the blood glucose levels observed during the 1 st and 2nd h when compared to single
were found to be 45.6% and 38.6%, respectively in diabetic rats Gliclazide treatment. The percentage changes in blood glucose
at 1st and 2nd h. Reduction in the blood glucose levels were level were 46.2% and 31.2% and 21.6% in the 4 th, 6 th and 8thh
found to be 8.4% and 11.7 % in the treatment with at the 1 nd respectively treatment in diabetic rats. This combination shows
and 2nd h respectively. The relatively maximum reduction of significant effect in the diabetic animals. The data’s were
blood glucose level was found to be 20.8% at 4th h. shown in Table. 2.

Table. 1. Effect of Valsartan on Sulfonylureas (Gliclazide) in normal rats.

S. No Time in Hrs Vehicle Control Gliclazide Treated Valsartan Treated Combination Therapy
1. 0 77.6 ± 1.3 76.90 ± 0.93 77.07 ± 1.17 77.08 ± 1.18
2. 1 76.4 ± 1.0 50.93 ± 1.10*** 72.50 ± 1.42 61.88 ± 0.93**
3. 2 76.9 ± 1.1 56.37 ± 0.87*** 67.87 ± 1.74*** 58.60 ± 0.86***
4. 4 77.6 ± 0.9 62.55 ± 1.18*** 62.50 ± 1.41*** 63.93 ± 0.69***
5. 6 77.3 ± 1.3 67.87 ± 1.41*** 73.47 ± 0.47 65.67 ± 0.92***

6. 8 77.5 ± 1.2 73.60 ± 0.46 76.60 ± 0.46 68.80 ± 1.30***

***Significant at p <0.001; ** P <0.01, Vehicle Control was Compared to Gliclazide treated, Valsartan treated and with the
Single dose combination therapy.

Table. 2. Effect of Valsartan on Sulfonylureas (Gliclazide) in Streptozotocin induced diabetic rats.

S. No Time in Hrs Diabetic Control Gliclazide Treated Valsartan Treated Combination Therapy
1. 0 327.2 ± 2.7 327.1 ± 2.7 326.3 ± 2.0 326.0 ± 1.9
2. 1 327.1 ± 2.2 177.9 ± 1.3*** 299.8 ± 3.5*** 139.7 ± 2.5***
3. 2 327.1 ± 2.4 200.9 ± 1.5*** 288.9 ± 3.7*** 159.9 ± 1.3***
4. 4 326.4 ± 2.4 224.9 ± 0.8*** 259.3 ± 3.6*** 176.8 ± 1.5***
5. 6 327.0 ± 2.1 247.5 ± 1.4*** 290.6 ± 1.9 *** 224.9 ± 1.6***
6. 8 327.9 ± 2.2 282.2 ± 2.0*** 303.5 ± 3.6*** 256.4 ± 1.5***

***Significant at p <0.001; Diabetic Control was compared to Gliclazide treated, Valsartan treated and with the Single dose
combination therapy.

4. DISCUSSIONS them Gliclazide is widely used drug because of its high

potency, prolonged action and lower incidence of side effects.
Diabetes mellitus is a chronic metabolic disorder characterized Hypertension is the commonly associated disorder with diabetic
by elevated blood glucose levels requires lifelong treatment. [11] patients. Angiotensin receptor blockers are one class of drugs
Oxidative stress has been associated with the pathogenesis of used in the treatment of hypertension associated with diabetics
chronic diabetic complications including cardiomyopathy.[12] patients. Therefore, there is a possibility for concomitant
Drug interactions are an important and wide source of administration of sulphonylureas with angiotensin receptor
medication errors. It is estimated that drug interaction results 6- blocker in patients with diabetes associated with hypertension.
30% of all adverse drug reactions.[13] Sulfonylureas are the Drug interactions result in alteration of pharmacokinetic
class of anti-diabetic agents that are most commonly prescribed parameters and therapeutic efficacy of concomitantly used
followed by insulin and biguanides. [14] Second generation drugs and hence require adjustment of their dosage schedule
Sulfonylureas should be prescribed for the patients suffering accordingly.[16, 17]
from type-II diabetes with ishemic heart disease. [15] Among

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 Chitra. K.S, et al.,/Int J Med Res., 2013; 1(7): 356-360 359

Figure. 1. Effect of Valsartan and Gliclazide normal animals

)
L1 0 0
d
/ Vehicl e C ontrol
g
m 80 G li clazide Tr eated
(
l Va lsat ran Treated
e
v
e 60 C om binat ion
L
e
s
o 40
c
u
l
G 20
d
o
o
l
0
B
r r r r r r
h h h h h h
0 1 2 4 6 8

Time in Hours

Figure. 2. Effect of Valsatran on Gliclazide in Streptozotocin induced dia betic rats

)
L4 00

/
d D iabeti c Control
g
m G li clazi de Treated
( 3 00
l V alsat ran Treated
e
v
e C om binat ion
L
e 2 00
s
o
c
u
l
1 00
G
d
o
lo
0
B
r r r r r r
h h h h h h
0 1 2 4 6 8

Time in Hours

Hence there is need for safety evaluation of Gliclazide on skeletal muscle glucose transport. [21] This indicates that when
its combination with respect to optimal blood glucose both the drug is administered together synergizes the activity of
maintenance. Based on the literature survey, there is a the Gliclazide drug.
possibility of drug- drug interactions between oral anti diabetic
drug Sulfonylureas and the angiotensin receptor blockers.[18] 5. CONCLUSION

Gliclazide produced hypoglycemia in normal rats, with
peak activity at the 1st h and 2nd hour. The maximum reduction
attained at the 1st h may be due to the simulation of initial rapid
release of insulin by Gliclazide, and due to the ability of
Gliclazide to increase the sensitivity of pancreatic β-cell to
glucose.[19] Gliclazide does not have any effect on prolonged
insulin release by blocking K+ channels in the pancreatic β
cells and increasing tissue uptake of glucose as extra pancreatic
mechanism.[20] The treated normal animals and diabetic rats
also show a non significant reduction of blood glucose level;
It may be concluded that during simultaneous administration of
Gliclazide and Valsartan, the adjustment of dose and frequency
of administration of Gliclazide may be needed in the presence
of Valsartan in the patients suffering from diabetes associated
with hypertension. Even though it may be considered as the
safe combination as it also alters the blood glucose levels so as
the complications in severe hypoglycemia.
6. REFERENCES

this mayepitrochlearis
in both be due to enhanced insulin
and soleus mediated
muscle. glucose
Therefore, transport [1]
angiotensin Sandhyarana. P., Krishnaprasad. P., Nareshkumara. N.,
Krishna Machary. P. (2011). Pharmacodynamic and
II receptor antagonism either acutely or chronically improves Pharmacokinetic drug Interaction of glipizide and
glucose tolerance, at least in part, because of an enhancement in benazepril in rabbits. International Journal of Pharma

www.ijmedres.com ©Copyright 2010 Medicobiological Research Publications. All rights reserved.

 Chitra. K.S, et al.,/Int J Med Res., 2013; 1(7): 356-360
World Research. 2(1): Jan – Mar, 1 – 11.
[2] American Diabetes Association: Diagnosis and
classification of diabetes mellitus. Diabetes Care 27: S5–
S10, 2004.
[3] Hines. L.E., and Murthy J.E. (2011). “Potentially Harmful
Drug –Drug Interactions in the Elderly: A Review”, The
American Journal of Geriatric Pharmacotherapy. 9(6),
364 – 377.
[4] Brahmankar and Sunil B. Jaiswal, “Biopharmaceutics and
Pharmacokinetics”, Ist Edition, 1995, 204-211.
[5] Ravindra Babu. P., Vanishree S., Sujatha. S., Kishore
Kumar. K. (2012). Effect of carvedilol on the
pharmacokinetics and pharmacodynamics of glipizide. Int
J Pharm Pharm Sci., 4(3): 133-138.
[6] Sarkar. A., Tiwari. A., Bhasin. P.S., Mitra M. (2009).
Pharmacological and Pharmaceutical Profile of
Gliclazide: A Review, J Appl Pharmaceut Scie. , 01: 11-
19.
[7] Ananya Sarkar, Ajay Tiwari, Parminder S. Bhasin and
Moloy Mitra. (2011). Pharmacological and
Pharmaceutical Profile of Gliclazide: A Review. J Appl
Pharmaceut Scie., 1(9): 11-19.
[8] John A D’Elia, George Bayliss, Bijan Roshan, Manish
Maski, Ray E. Gleason, Larry A. Weinrauch. (2011).
Diabetic microvascular complications: possible targets for
improved macrovascular outcomes. Int J Nephrology and
Renovascular Disease., 4.
[9] Kang J.J., Toma. I, Sipos. A, McCulloch Fand Peti-
Peterdi. J. (2006). Imaging the rennin-angiotensin system:
An important target of anti-hypertensive therapy.
Advanced Drug Delivery Review., 58: 824-833.
[10] Flesch. G., Muller. P and Lloyd. P. (1997). Absolute
bioavailability and pharmacokinetics of an angiotensin II
receptor antagonist, in man. European J Clin Pharmacol.
52: 115 - 120.
[11] Suresh Janadri, Ramachandra. S.S, Kharya. M.D. (2009).
Influence of itraconazole on antidiabetic effect of
thiazolidinedione in diabetic rats. International Journal of
Pharm and Pharmaceut Scie., 1(1): 1-8.
[12] Jang, J.H., Surh. Y.J., (2003). Potentiation of cellular
antioxidant capacity by Bcl-2: implications for its
antiapoptotic function. Biochem Pharmacol., 66: 1371-
Disclaimer: Statements, information, inferences, observations and findings etc., stated in the International Journal of Medicobiological
Research are attributed to the authors and do in no way imply to Journal. Queries related to articles should be directed to authors.
www.ijmedres.com ©Copyright 2010 Medicobiological Research Publications. All rights reserved.
360
1379.
[13] Bista. D, Palaian. S, Shankar. P.R, Prabhu. M.M, Paudel
R, Mishra P. (2006). Kathmandu Univ Med J., 4: 421-
430.
[14] Nadeem Siddiqui., Asif Husain., Lakshita Chaudhry.,
Shamsher Alam., Moloy Mitra and Parminder S. Bhasin.
(2011). Pharmacological and Pharmaceutical Profile of :
A Review. J Appl Pharmaceut Scie., 1(4): 12-19.
[15] Denis Xavier., Nagarani. M.N. and M.V. Srishyla. (1999).
Drug Utilization study of antihypertensive and
antidiabetic in Indian referral hospitals. Ind J Pharmacol.,
31: 241-242.
[16] Greenfield. M.S., Doberne. L., Rosenthal. M., Verman
H.J and G.M. Reaven. (1982). Lipid metabolism in non
insulin dependent Diabetes mellitus; effect of glipizide
therapy. Arch Intern Med., 142(8): 1498-1500.
[17] Gopala Krishna Murthy. T.E., Candasamy Mayuren.
(2008). Influence of irbesartan on the pharmacodynamics
and pharmacokinetics of Gliclazide in rats and rabbits.
Journal of Pre-Clinical and Clinical Research., 2(2): 127-
132.
[18] Tingting Wu, Zhe Dong, Jing Geng, Yingying Sun,
Guanghui Liu, Weiqiang Kang,Yun Zhang, Zhiming Ge.
(2011). protects against ER stress-induced myocardial
apoptosis via CHOP/Puma signaling pathway in
streptozotocin-induced diabetic rats. European Journal of
Pharmaceutical Sciences., 42: 496–502.
[19] Karl F. Hilgers., Andrea Hartner., Markus Porst., Roland
Veelken., Johannes F.E. Mann. (2001). Angiotensin II
Type 1 Receptor Blockade Prevents Lethal Malignant
Hypertension, Circulation., 104: 1436-1440.
[20] Wu T., Dong. Z., Geng. J., Sun. Y., Liu. G., Kang. W.,
Zhang. Y and G. Zhiming. (2011). Protects against ER
stress-induced myocardial apoptosis via CHOP/Puma
signaling pathway in streptozotocin-induced diabetic
rats”, Euro J Pharmaceut Scie., 42: 496-502.
[21] Satyanarayana .S and Kilari E.K. (2006). Influence of
nicorandil on the pharmacodynamics and
pharmacokinetics of Gliclazide in rats and rabbits.
Molecular and cellular biochemistry., 291: 101-105.
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 Research Article ISSN 2277-3657
Available online at www.ijpras.com
International Journal of
Volume 2, issue 1 (2013),49-55 Pharmaceutical Research &
Allied Sciences

Pharmacokinetic Interactions of Glipizide with Esomeprazole in

Normal, Diabetic and Ulcerative Rats
Jaideep Singh1*, Samir C. Patel2
Research scholar, JJT University, Jhunjhune, Rajasthan, India1
Kalol institute of pharmacy, Kalol, Gujarat, India2

e-mail: jaydeepsingh21@gmail.com

Subject: Pharmacology
Abstract
The present study was carried out to evaluate the drug-drug interactions between esomeprazole and
glipizide. Interaction of esomeprazole (Eso), the known antiulcer drug with antidiabetic agent, glipizide
(Gli) was evaluated in healthy, diabetic and ulcerative rats. Single day (SD) and multiple day (MD)
pharmacokinetic studies were performed for glipizide and esomeprazole in normal, diabetic and ulcerative
animals. Blood samples were collected at 0, 0.25, 0.5, 1, 2, 4, 8 and 24 hours (hr) and pharmacokinetic
parameters were determined. Both single and multiple days treatment of glipizide has shown no effect on
pharmacokinetic profile of esomeprazole, while esomeprazole influenced the pharmacokinetic properties of
glipizide in both normal and diabetic rats. This may be due to inhibition of CYP (cytochrome P-450)
enzyme by esomeprazole, the enzyme through which glipizide gets metabolized. The findings of the
present study suggested that there is potential pharmacokinetic interaction between glipizide and
esomeprazole in rats.

Key words: Glipizide, Esomeprazole, Streptozotacin, Pharmacokinetic.

Introduction
In many chronic ailments, the multi drug therapy
may be advocated to mitigate the severity of or
to avoid the development of possible resistance.
There is every possibility of occurrence of drug-
drug interactions when multiple drugs were
administered simultaneously. These interactions
may be so severe to cause mortality or may
nullify the therapeutic efficacy of the treatment.
Drug interactions have become a significant
issue in health care system. These drug
interactions can be explained by alteration in the
pharmacokinetic parameters including inhibition
or induction of metabolic enzymes or by
alterations in pharmacodynamic properties of
one or both of the drugs. Many of the major
pharmacokinetic interactions occur due to
induction or inhibition of hepatic cytochrome
P450 enzymes1,2. There are certain patients who
may be suffering with more than one disease at a
time, which may require chronic treatment such
as diabetes and gastric ulcer. As both diseases
require chronic treatment or chronically used as
prophylaxis. In any case, it can create a scenario
where one has to use multiple drug therapy for
such diseases. This will lead to drug-drug
interactions, where one drug may influence the
pharmacokinetic or pharmacodynamic profile of
the other3.
Diabetes is a metabolic disorder of multiple
etiologies characterized by chronic
hyperglycemia with disturbances of
carbohydrate, fat and protein metabolism
resulting from defects in insulin secretion,
insulin action, or both. There are reports that
several patients suffering from diabetes are prone
to peptic ulcer infections4. Antiulcer drugs such
as ranitidine, famotidine, omeprazole and

49
 Available online at www.ijpras.com
lansoprazole potentiates the action of many
sulfonylureases, when they are used
concomitantly for a prolong period of time5,6,7.
Glipizide is an oral hypoglycemic agent, which
is a commonly prescribed drug for the treatment
of patients with type II diabetes mellitus8 and it
is extensively metabolized in the liver by
CYP2C99 and CYP3A410,11,12. Esomeprazole is a
Proton pump inhibitor and S-isomer of
omeprazole. Esomeprazole is extensively
metabolized by CYP3A4 and CYP2C19 in
liver13.
On perusal of literature survey, we found that the
interaction of glipizide and esomeprazole has not
been elucidated. Therefore, the present study was
conducted to assess the interaction between
esomeprazole and glipizide in normal, diabetic
and ulcerative rats.
Materials and Methods
Drugs: Esomeprazole was purchased from
Sigma–Aldrich Co, St Louis, MO, USA and
glipizide was obtained as gift samples from
Matrix Pvt. Ltd, Hyderabad. All other chemicals
used were of analytical grade.
Experimental animals: Wistar rats weighing
200 to 250 g were used for the present study.
Animals were housed under a standard 12 hr:
12hr light/dark cycle and were provided with
food and water ad libitium. Animals were
acclimated to laboratory conditions before
testing. The animal protocol was approved by the
Institutional Animal Ethical Committee of Kalol
institute of pharmacy, India.
Experimental procedures:
Streptozotacin (STZ) induced diabetes14: At
neonatal stage, STZ was administered at day 2
and day 3 of birth at a dose of 45 mg/kg in citrate
buffer at pH 4.5, which result in diabetic
condition. At the end of 8th week of their age,
oral glucose tolerance test was done at a dose of
3 g/kg of glucose to evaluate the diabetic
condition in rats. The rats which have 45% high
glucose AUC compared to normal control were
selected for the study.
Indomethacin induced chronic gastric ulcer15:
The rats were treated with indomethacin orally at
a dose of 1 mg/kg per day for a period of 12
weeks. At the end of 12 weeks, animals were
selected for the study.
Pharmacokinetic interaction study in normal,
diabetic and ulcerative rats:
Wistar rats were randomly distributed into
different groups of six animals in each group.
They were housed in well ventilated
polypropylene cages and maintained on uniform
diet and temperature with 12 hr light and dark
cycle. Glipizide was administered at a dose of 50
mcg/kg and esomeprazole at a dose of 30 mg/kg,
orally to their respective groups. These animals
were mainly divided into two sub groups as
follows: Normal and diseased animals. In normal
rats, Group 1 was vehicle control, which
received vehicle. Group 2 and 3 were served as
treatment groups, which received esomeprazole
and glipizide respectively. Group 4 was served
as treatment group (SD), which received
esomeprazole, followed by glipizide after 30
minutes. Group 5 was served as treatment group
(SD), which received glipizide, followed by
esomeprazole after 30 minutes. Group 6 was
served as treatment group (MD), which received
esomeprazole for 8 days, followed by glipizide
after 30 minutes on 8th day. Group 7 was served
as treatment group (MD), which received
glipizide for 8 days, followed by esomeprazole
after 30 minutes on 8th day.
In disease rats, Group 1 and 2 were served as
diabetic and ulcerative control, which received
vehicle. Group 3 rats were diabetic which
received glipizide and group 4 rats were
ulcerative which received esomeprazole. Group
5 rats were diabetic (SD), which received
esomeprazole, followed by glipizide after 30
minutes. Group 6 rats were ulcerative (SD),
which received glipizide, followed by
esomeprazole after 30 minutes. Group 7 rats
were diabetic (MD), which received
esomeprazole for 8 days, followed by glipizide
after 30 minutes on 8th day. Group 8 rats were
ulcerative (MD), which received glipizide for 8
days, followed by esomeprazole after 30 minutes
on 8th day.
All the animals were over night (12 hours) fasted
with water ad libitum. Animals were
administered with their respective treatments.
Blood was collected at 0, 0.25, 0.5, 1, 2, 4, 8 and
24th hour. Samples were centrifuged at 8000 rpm
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for 10 minutes, plasma was collected and
subjected for high performance liquid
chromatography (HPLC) analysis.
Pharmacokinetic data analysis16: The
maximum plasma concentration (Cmax), time
needed to reach the maximum plasma
concentration (Tmax), area under the
concentration– time curve (AUC0–24), mean
residence time (MRT), elimination rate constant
(Kel) and half life (T1/2) were calculated using
non compartmental pharmacokinetic model of
WinNonlin-5.3.
Statistical analysis: All the means are presented
with their standard error mean (mean ±SEM).
The pharmacokinetic parameters were compared
using one-way ANOVA, followed by Dunnett
test.
Results
The mean plasma levels were evaluated for
glipizide and esomeprazole alone and their
combinations in both normal and diseased
condition. In single dose study, Glipizide alone
has shown significant increase in Cmax in both
normal and diabetic condition (table-1 and 2).
Single day treatment with esomeprazole
potentiate the pharmacokinetic profile of
glipizide in both normal, (AUC, 77.44±4.13 vs.
58.12±2.51, P<0.05), (Cmax, 8.54±0.27 vs.
6.73±0.45, P<0.01), (T1/2, 4.34±0.16 vs.
3.23±0.24, P<0.01) and diabetic (AUC,
83.77±5.82 vs. 65.00±4.77, P<0.05), (Cmax,
9.18±0.43 vs. 7.35±0.33, P<0.01), (T1/2,
4.11±0.09 vs. 3.37±0.13, P<0.001) rats. While
glipizide has not shown any significant
improvement in pharmacokinetic properties of
esomeprazole.
In multiple days treatment, esomeprazole shown
significant increase in the pharmacokinetic
parameters of glipizide in both normal (AUC,
106.42±6.15 vs. 58.12±2.51, P<0.001), (Cmax,
11.92±0.22 vs. 6.73±0.45, P<0.001), (T1/2,
4.71±0.10 vs. 3.23±0.24, P<0.001) and diabetic
(AUC, 104.91±6.73 vs. 65.00±4.77, P<0.01),
(Cmax, 12.05±0.30 vs. 7.35±0.33, P<0.001), (T1/2,
4.98±0.06 vs. 3.37±0.13, P<0.001) rats. While
glipizide has not shown any significant
improvement in pharmacokinetic properties of
esomeprazole

Tables

Table 1: Mean pharmacokinetic parameters of glipizide alone and during esomeprazole treatment in
normal rats
Glipizide+Esomeprazole Glipizide+Esomeprazole
Parameters Glipizide
(SD) (MD)
Cmax (mcg/ml) 6.73±0.45 8.54±0.27** 11.92±0.22***

Tmax (hr) 4.00±0.00 4.00±0.00 4.00±0.00

AUC 0-24h (hr*mcg/mL) 58.12±2.51 77.44±4.13* 106.42±6.15***

T1/2 (hr) 3.23±0.24 4.34±0.16** 4.71±0.10***

Kel (1/hr) 0.219±0.02 0.160±0.01* 0.147±0.01**

MRT (hr) 5.76±0.01 5.96±0.05 5.92±0.09

Mean ±SEM (n=6), ***p<0.001, **p<0.01, *p<0.05 compared to glipizide control.

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Table 2: Mean pharmacokinetic parameters of glipizide alone and during esomeprazole treatment in
diabetic rats
Glipizide+Esomeprazole Glipizide+Esomeprazole
Parameters Glipizide
(SD) (MD)
Cmax (mcg/ml) 7.35±0.33 9.18±0.43** 12.05±0.30***

Tmax (hr) 4.00±0.00 4.00±0.00 4.00±0.00

AUC 0-24h (hr*mcg/mL) 65.00±4.77 83.77±5.82* 104.91±6.73**

T1/2 (hr) 3.37±0.13 4.11±0.09*** 4.98±0.06***

Kel (1/hr) 0.207±0.012 0.169±0.001** 0.139±0.002***

MRT (hr) 5.80±0.25 6.00±0.07 5.95±0.10

Mean ±SEM (n=6), ***p<0.001, **p<0.01, *p<0.05 compared to glipizide control.

Table 3: Mean pharmacokinetic parameters of esomeprazole alone and during glipizide treatment in
normal rats
Esomeprazole+Glipizide Esomeprazole+Glipizide
Parameters Esomeprazole
(SD) (MD)
Cmax (mcg/ml) 1.22±0.04 1.36±0.03 1.23±0.05

Tmax (hr) 1.00±0.00 1.00±0.00 1.00±0.00

AUC 0-24h (hr*mcg/mL) 11.25±0.92 11.91±1.52 10.12±0.79

T1/2 (hr) 3.51±0.23 3.63±0.27 3.45±0.18

Kel (1/hr) 0.199±0.01 0.193±0.01 0.202±0.01

MRT (hr) 5.39±0.16 5.34±0.29 5.16±0.15

Mean ±SEM (n=6), ***p<0.001, **p<0.01, *p<0.05 compared to esomeprazole control.

Table 4: Mean pharmacokinetic parameters of esomeprazole alone and during glipizide treatment in
ulcerative rats
Esomeprazole+Glipizide Esomeprazole+Glipizide
Parameters Esomeprazole
(SD) (MD)
Cmax (mcg/ml) 1.53±0.06 1.58±0.05 1.63±0.06

Tmax (hr) 1.00±0.00 1.33±0.33 1.00±0.00

AUC 0-24h (hr*mcg/mL) 13.49±1.20 13.17±1.04 13.97±1.18

T1/2 (hr) 3.57±0.25 3.56±0.15 3.66±0.22

Kel (1/hr) 0.196±0.01 0.195±0.01 0.191±0.01

MRT (hr) 5.32±0.12 5.34±0.22 5.42±0.18

Mean ±SEM (n=6), ***p<0.001, **p<0.01, *p<0.05 compared to esomeprazole control.
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Figures

Fig.1. Plasma concentrations time curves of (Gli) glipizide following its oral administration at 50
mcg/kg in control and (Eso) esomeprazole (30 mg/kg) pre-treated (SD & MD) normal (A) and
diabetic (B) rats. Data are expressed as mean±SEM in (n = 6) rats.

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Fig.2. A, B, C and D, E, F represent pharmacokinetic parameters in normal and diabetic rats

respectively. Half life, Cmax and AUC of glipizide following its oral administration at 50 mcg/kg in
control and esomeprazole (30 mg/kg) pre-treated (SD & MD) normal (A,B,C) and diabetic (D,E,F)
rats respectively. Data are expressed as mean±SEM in (n = 6) rats.

Discussion
Chronic elevation of blood glucose levels leads
to many co-existing complications like diabetic
retinopathy, diabetic neuropathy, delay in
healing of gastric ulcer, diabetic foot ulcer. Drug
therapy in Type II diabetes becomes more
complex as many individuals are on multiple
drug therapy and administer many drugs during
the same period of time to treat secondary
diabetic complications17. A closer monitoring
and supervision of drug therapy is required so
that drug related problems can be prevented or
detected at an early stage. An increasing number
of drug related problems are caused by drug
interactions17. Currently, the management of
type II diabetes becoming more complex since
the recommended global approach of
combination drug therapy has increased the risk
of pharmacokinetic interactions in patients with
diabetes18. The activity of one drug could alter
the pharmacokinetics of another drug and it may
be due to risk of the enzyme inverse reaction
upon the plasma levels of concomitantly
administered drugs19.
Esomeprazole, the (S)-isomer of omeprazole, is
the first proton pump inhibitor developed as a
single isomer for the treatment of acid-peptic
diseases. Esomeprazole is extensively
metabolized by CYP3A4 and CYP2C19
isoenzyme in the liver13. Glipizide is highly
potent second generation sulfonylurea derivative
which is used for the treatment of type II
diabetes mellitus. Glipizide is extensively
metabolized in the liver by CYP2C99 and
CYP3A410,11,12. Alteration in pharmacokinetic
profile of esomeprazole and glipizide was
assessed by interaction between these drugs in
both normal and diseased rats. Single dose study
showed that glipizide administration did not
potentiate the pharmacokinetic parameters of
esomeprazole. Glipizide has not shown any
significant improvement in absorption,
metabolism and excretion of esomeprazole in
both healthy and diseased rats, which indicates
no significant interaction occurred. While, single
dose administration of esomeprazole stimulated
the pharmacokinetic profile of glipizide in both
healthy and diabetic rats which indicates an
inhibition of glipizide metabolism leading to
increased AUC and high plasma levels of
glipizide in both normal and diabetic rats. This
confirmed interaction occurred at absorption site.
Prior administration of esomeprazole further
increases the half life and decreases the Kel when
compared with glipizide alone which indicates
interaction occurred at metabolism and excretion
site also. In multiple dose study, repeated dosing
of glipizide did not influence the
pharmacokinetic profile of esomeprazole in both
healthy and ulcerative rats. Hence, interaction at
absorption, metabolism and excretion site has
been ruled out. While, seven days administration
of esomeprazole increased the Cmax and also
shown significant increase in AUC of glipizide
which indicate potential absorption profile of
glipizide in both normal and diabetic condition.
On metabolism and excretion, esomeprazole has
shown significant increase in half life and
decreases the Kel when compared with glipizide
alone which indicates interaction occurred at
metabolism and excretion site also. These data
confirmed that concomitant administration of
glipizide and esomeprazole might result in
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 Available online at www.ijpras.com
pharmacokinetic interaction. The above results
suggested that esomeprazole produces
synergistic effect with glipizide because
esomeprazole increased the plasma levels of
glipizide in both normal and diabetic rats. The
mechanism involved in this interaction may be
the inhibition of CYP3A4 enzyme, the enzyme
responsible for metabolizing glipizide by
esomeprazole.
“Cite this article”
J. Singh, S.Patel “Pharmacokinetic Interactions
of Glipizide with Esomeprazole in Normal,
Diabetic and Ulcerative Rats.”l Int. J. of Pharm.
Res. & All. Sci.2013; Volume 2, Issue 1,49-55
References:
1. Tanaka, E., Clinically important drug
interactions: role of CYP enzymes, J. Clin.
Pharm. Ther., 1998, 23(6), 403-16
2. Bertilsson, L., Lou, Y.Q., Du, Y.L.,
Pronounced differences between native
Chinese and Swedish populations in the
polymorphic hydroxylations of debrisoquine
and S-mephenytoin, Clin. Pharmacol. Ther.,
1992, 51, 388–97
3. Alan S., Nies., Stephen., Spielberg P.
Principles of therapeutics: Goodman and
Gilman’s the pharmacological basis of
therapeutics. 10th Edition. New york:
Megraw Hill; 2001; 45-65
4. Lai, K.C., Lam, S.K., Chu, K.M.,
Lansoprazole for the prevention of
recurrences of ulcer complications form long-
term low-dose aspirin use, N. Eng. J. Med.,
2002, 346, 2033-38
5. Krishnaiah, Y.S.R., Satyanarayana, S.,
Visweswaram, D., Influence of ranitidine on
the hypoglycemic activity of tolbutamide and
glibenclamide in rabbits, Ind. J. Physiol.
Pharmacol., 1994, 38, 316-18.
6. Rajendra, S.V., Influence of lansoprazole on
the hypoglycaemic activity of oral
antidiabetic agents in healthy albino rats,
Acta Pharmaceutica Turcica, 2004, 46, 95-99
7. Kumar, V., Venakat, R.N., Ramachandra, S.,
Influence of omeprazole on hypoglycaemic
activity of glibenclamide and tolbutamide in
normal albino rabbits, Acta Pharmaceutica
turcica, 2000, 42(4), 135-38
8. Verma, R.K., Garg, S., Development and
evaluation of osmotically sustained oral drug
delivery systems of glipizide, Eur. J. pharm.
Biopharm., 2004, 57, 513-25
9. Kidd, R.S., Straugh, A.B., Meyer, M.C.,
Blaisdell, J., Goldstein, J.A., Dalton, J.T.,
Pharmacokinetics of chlorpheniramine,
phenytoin, glipizide and nifedipine in an
individual homozygous for the CYP2C9*3
allele, Pharmacogenetics, 1999, 9, 71-80
10. Peart, G.F., Boutagy, J., Shenfield, G.M., The
metabolism of glyburide in subjects of
known debrisoquin phenotype, Clin. Pharm.
Ther., 1989, 20, 283-95
11. Wensing, G., Glipizide: an oral
hypoglycemic drug, Am. J. Med. Sci., 1989,
298, 69-71
12. Brian W.R., Metabolic drug interactions.
Philadelphia: Lippincott Williams & Wilkins;
2000
13. Andersson, T., Hassan-Alin, M., Hasselgren,
G., Rohss, K., Drug interaction studies with
esomeprazole, the (S)-isomer of omeprazole,
Clin. Pharmacokinet., 2001, 40, 523-37
14. Pascoe, W.S., Jenkins, A.B., Kusunoki, M.,
Storlien, L.H., Insulin action and
determinants of glycaemia in a rat model of
Type 2 (non-insulin-dependent) diabetes
mellitus, Diabetologia, 1992, 35(3), 208-15
15. Xiang, Z., Jian-Min, Si., Huai-De, H.,
Chronic gastritis rat model and role of
inducing factors, World J. Gastroenterol.,
2004, 10(21), 3212-14
16. Prashanth, S., Kumar, A.A., Madhu, B.,
Rama, N., VidyaSagar, J., Pharmacokinetic
and pharmacodynamic drug interactions of
carbamazepine and glibenclamide in healthy
albino wistar rats, J Pharmacol.
Pharmacother., 2011, 2(1), 7–10
17. Thirumurugu, S., Parthasarathy, V.,
Arumainayagam, D.C., Manavalan, R.,
Bioavailability studies of Pioglitazone with
Antacid –An Invivo Evaluation in Human
Volunteers, International Journal of
Preclinical and Pharmaceutical Research,
2011, 2(2), 76-80
18. Sudhir, N., Umathe., Pankaj, V.D., Quercetin
pretreatment increases the bioavailability of
pioglitazone in rats: Involvement of CYP3A4
inhibition, Biochemical Pharmacology, 2008,
75, 1670–76
19. Michael, A., Wynalda, J., Hutzler, M., Invitro
metabolism of clidamycin in Human liver
and intestinal microcosms, Drug metabolism
and disposition, 2003, 31(7), 878-87
55
Nama : Sahrul Gafur
Nim : 1608060017

Penyusun jurnal : Mohan Komar ,Deepak Kumar Dash, Bibekananda Meher Dan
Trillochan Satapaty

Single dose drug interaction study between anti-hypertensive drug valstran

on antidiabetic effect of sulfonylureas in normal and streptozotocin induced
diabetic rats
Intraksi obat dosis tunggal antara pembelajaran anti-hipertensi obat
valstran dalam anti diabetic dari efek sulfonylurea dalam normal dan
streptozoctin di indikasi tikus diabetes

ABSTRAK
Dalam beberapa kejadian terungkap bahwa seorang pasien bisa menderita
lebih dari satu penyakit pada suatu waktu. Di kondisi seperti itu, lebih dari dua
obat digunakan dalam pengobatan penyakit. Makanya, narkoba – narkoba
interaksi tidak dapat diprediksi dan tidak dapat dihindari dalam terapi multi-obat.
Diabetes mellitus adalah gangguan metabolisme yang ditandai dengan
hiperglikemia dan metabolisme karbohidrat, protein dan lemak gangguan.
Tujuan dari penelitian ini adalah untuk menyelidiki keamanan, keandalan
Valsartan pada anti efek diabetes dari Gliclazide pada tikus normal dan diabetes.
Diabetes diinduksi oleh lajang injeksi intraperitoneal Streptozotocin 50mg / kg
pada tikus. Sampel darah dikumpulkan dari vena ekor pada interval waktu 0, 1, 2,
4, 6 dan 8 jam dan kadar glukosa darah diperkirakan. Gliclazide menghasilkan
aktivitas hipoglikemia dalam dosis yang tergantung pada normal dan diabetes
kondisi. Dari hasil itu diketahui bahwa di hadapan Valsartan, Gliclazide tidak
menghasilkan tindakan awal dan mempertahankan aktivitas anti diabetes pada
kelompok yang diinduksi diabetes. Karenanya, dari penelitian disimpulkan bahwa
dosis dan / atau frekuensi pemberian Gliclazide memiliki sedikit atau tidak ada
efek ketika kedua obat telah digunakan secara bersamaan.
Desain penelitian
Eksperimental desain
Metode penelitian
Tikus dibagi menjadi delapan kelompok yang terdiri dari 6 hewan di Indonesia
masing-masing kelompok sebagai berikut:
1. Grup normal
Kelompok I :Tikus kontrol hanya diberi 0,5% Methyl Cellulose (MC).
Kelompok II : Hewan normal yang diobati dengan Gliclazide(1,44mg / 200g).
Kelompok III :Hewan normal yang dirawat dengan Valsartan (30mg / kg).
Kelompok IV :Hewan normal yang dirawat dengan Valsartan dan Gliclazide
(terapi kombinasi).
Kelompok diabetes
Kelompok I: Kontrol diabetes (STZ 60 mg / kg) diberikan hanya 0,5% Metil
Selulosa (MC).
Kelompok II: tikus diabetes yang diobati dengan Gliclazide (1,44 mg / 200 g).
Kelompok III: Tikus diabetes diobati dengan Valsartan (30 mg / kg).
Kelompok IV: Tikus diabetes yang diobati dengan keduanya dan Gliclazide
(terapi kombinasi).
Interaksi secara farmakodinamik
Gliclazide dan Valsartan dianggap sebagai kombinasi yang aman karena dapat
mengubah kadar glukosa darah komplikasi pada hipoglikemia berat
Golongan obat
Gliklazide (sulfenilurea): merangsang sekresi insulin pada pangkreas
Valstran (angiotensin receptor bloker): menghambat efek angiotensin II yang
menyebabkan pembuluh bdarah menyempit.
Rute pemberian obat
Gliklazide (oral)
Valstran (oral)
Kesimpulan
Dapat disimpulkan bahwa selama administrasi simultan Gliclazide dan Valsartan,
penyesuaian dosis dan frekuensi administrasi Gliclazide mungkin diperlukan di
hadapan Valsartan pada pasien yang berhubungan dengan diabetes dengan
hipertensi. Meskipun dapat dianggap sebagai kombinasi yang aman karena
juga mengubah kadar glukosa darah komplikasi pada hipoglikemia berat
 Pharmacokinetic Interactions of Glipizide with Esomeprazole in
Normal, Diabetic and Ulcerative Rats
Interaksi Farmakokinetik Glipizide dengan Esomeprazole di
Tikus Normal, Diabetes dan Ulseratif
Abstrak
Penelitian ini dilakukan untuk mengevaluasi interaksi obat-obat antara
esomeprazole dan glipizide. Interaksi esomeprazole (Eso), obat antiulcer yang
dikenal dengan agen antidiabetes, glipizide (Gli) dievaluasi pada tikus yang sehat,
diabetes dan ulseratif. Satu hari (SD) dan beberapa hari (MD) studi
farmakokinetik dilakukan untuk glipizide dan esomeprazole dalam keadaan
normal, diabetes dan ulseratif binatang. Sampel darah dikumpulkan pada 0, 0,25,
0,5, 1, 2, 4, 8 dan 24 jam (jam) dan farmakokinetik parameter ditentukan.
Pengobatan glipizide tunggal dan beberapa hari tidak menunjukkan efek apa pun
profil farmakokinetik esomeprazole, sedangkan esomeprazole memengaruhi sifat
farmakokinetik dari glipizide pada tikus normal dan diabetes. Ini mungkin karena
penghambatan CYP (cytochrome P-450) enzim oleh esomeprazole, enzim yang
melaluinya glipizide dimetabolisme. Temuan dari penelitian ini menunjukkan
bahwa ada interaksi farmakokinetik potensial antara glipizide dan esomeprazole
pada tikus.
Metode Penelitian
Experimental: Esomeprazole dibeli dari Sigma – Aldrich Co, St Louis, MO,
USA dan glipizide diperoleh sebagai sampel hadiah dari Matriks Pvt. Ltd,
Hyderabad. Semua bahan kimia lainnya yang digunakan adalah kelas analitis
Desain Penelitian
Experimental Desain
Tikus Wistar dengan berat 200 hingga 250 g digunakan untuk penelitian ini.
Hewan ditempatkan di bawah standar 12 jam: 12 jam siklus terang / gelap dan
dilengkapi dengan makanan dan air ad libitium. Binatang itu terbiasa
dengan kondisi laboratorium sebelumnya pengujian. Protokol hewan telah
disetujui olehKomite Etik Hewan Institusional Kalol lembaga farmasi, India.
Golongan obat
Glipizide (sulfenilurea): merangsang sekresi insulin pada pangkreas
Rute pemberian
Oral
farmakokinetik
Glipizide tidak mempengaruhi profil farmakokinetik esomeprazole di keduanya
tikus sehat dan ulseratif.
Kesimpulan
Sampel darah dikumpulkan pada 0, 0,25, 0,5, 1, 2, 4, 8 dan 24 jam (jam) dan
farmakokinetik parameter ditentukan. Pengobatan glipizide tunggal dan beberapa
hari tidak menunjukkan efek apa pun profil farmakokinetik esomeprazole,
sedangkan esomeprazole memengaruhi sifat farmakokinetik dari glipizide pada
tikus normal dan diabetes. Ini mungkin karena penghambatan CYP (cytochrome
P-450) enzim oleh esomeprazole, enzim yang melaluinya glipizide
dimetabolismeTemuan dari penelitian ini menunjukkan bahwa ada interaksi
farmakokinetik potensial antara glipizide dan esomeprazole pada tikus.