Biopharmaceu,cs and

Pharmacokine,cs
Pamela Berilyn So, RPh, Msc
 Pharmaceu,cals
Approved by the FDA
Ac,ve Ingredient
Dosage Form
Route of Administra,on

in vivo performance
Safety and Ecacy
 Importance of Formula,on
Route: (oral, IV, subQ, transdermal, etc.)
Drug release: predictable and characterizable
Site of ac,on: drug concentra,on>MEC
Pharmacologic response
 Bioavailability
A measure of systemic availability of a drug
The rate and extent to which a drug
reaches the systemic circula,on
Drug Animal/ Response
product Human

Isoproterenol- increase in HR if given IV, given

orally at the same dose: no eect
 Bioavailability
Nature of the drug molecule
The route of delivery
The formula,on of the dosage form

Therapeu,cally eec,ve
Toxic
Has no apparent eect at all.
 Biopharmaceu,cs
The science that examines the
interrela,onship of the physicochemical
proper,es of the drug, the dosage form in
which the drug is given, and the route of
administra,on on the rate and extent of
systemic drug absorp9on.
 Biopharmaceu,cs
Involves factors that influences:
(1) the stability of the drug within the
drug product (DP)
(2) the release of the drug from the DP
(3) the rate of dissolu9on/release of the drug
at the absorp9on site
(4) the systemic absorp,on of the drug
 Biopharmaceu,cs
Scheme demonstra,ng the dynamic
rela,onship between the drug, the drug
product, and the pharmacologic eect.
 Pharmacokine,cs
The science of the kine,cs of drug absorp,on,
distribu,on, and elimina,on (M+E)
Drug Disposi9on (D+E)
 Pharmacokine,cs
Experimental approach
development of biologic
sampling techniques
analy,cal methods for the measurement of
drugs and metabolites
procedures that facilitate data
collec9on and manipula9on
 Pharmacokine,cs
Theore9cal approach
development of pharmacokine,c
models that predict drug disposi9on
a[er drug
administra9on
 Theore,cal approach
Sta,s,cal methods
Used for pharmacokine,c parameter
es9ma9on and data interpreta9on
ul,mately for the purpose of designing and
predic,ng op9mal dosing regimens.
Applied to pharmacokine,c models to
determine data error and structural model
devia9ons.
 Classical Pharmacokine,cs
A study of theore9cal models focusing mostly
on model development and parameteriza,on.
 Clinical Pharmacokine,cs
Applica,on of pharmacokine,c methods to
drug therapy
Involves a mul,disciplinary approach to
individually op,mized dosing strategies based
on the pa,ent's disease state and pa,ent-
specific considera,ons.
 Clinical Pharmacokine,cs
During the drug development process, large
numbers of pa,ents are tested to determine
op,mum dosing regimens
May result in either a subtherapeu,c (drug
concentra,on<MEC) or toxic response (drug
concentra,ons>MTC )

Require dose adjustment

 Pharmacokine,cs
TDM for potent drugs with narrow therapeu,c
range
op,mize ecacy
prevent any adverse toxicity
Monitor plasma drug concentra,ons
(theophylline)
Specific pharmacodynamic endpoint such as
prothrombin cloang ,me (warfarin )
 Pharmacodynamics
The rela,onship between the drug
concentra,on at the site of ac,on (receptor)
and pharmacologic response
Includes biochemical and physiologic eects
that influence the interac9on of drug with the
receptor
 Toxicokine,cs
The applica,on of pharmacokine,c principles
to the design, conduct, and interpreta,on of
drug safety evalua9on studies and in
valida,ng dose-related exposure in animals
Toxicokine,c studies are performed in animals
during preclinical drug development
 Clinical Toxiclogy
The study of adverse eects of drugs and toxic
substances (poisons) in the body.
Pharmacokine,cs of a drug in an overmedicated
(intoxicated ) pa,ent may be very dierent from
the pharmacokine,cs of the same drug given in
lower therapeu,c doses.
Drugs frequently involved in toxicity cases:
acetaminophen, salicylates, morphine, and TCAs
Measurement of Drug Concentra,ons
Invasive methods
blood, spinal fluid, synovial fluid, ,ssue
biopsy, or any biologic material that
requires parenteral or surgical interven,on
in the pa,ent
Non invasive methods
urine, saliva, feces, expired air, or any
biologic material w/o parenteral or surgical
interven,on
Drug Levels in Blood, Plasma, or Serum
Measurement of drug levels in the blood,
serum, or plasma is the most direct approach
to assessing the pharmacokine,cs of the drug
in the body.
Whole blood RBC, WBC, platelets, albumin
Serum blood is allowed to clot, centrifuged
Plasma add an,coagulant, centrifuged
Drug Levels in Blood, Plasma, or Serum
The protein content of serum and plasma:
NOT the same
Plasma perfuses all the ,ssues of the body,
including the cellular elements in the blood.
Assume: changes in the drug concentra,on in
plasma will reflect changes in 9ssue drug
concentra,ons
 Plasma Level Time Curve
Generated by obtaining the drug
concentra,on in plasma samples taken at
various 9me intervals a[er a drug product is
administered
The concentra9on of drug in each plasma
sample is ploIed on a graph paper against the
corresponding 9me at which the plasma
sample was obtained
 Plasma Level Time Curve
Absorp,on is
more rapid than
elimina,on
MEC; MTC
Onset ,me
Intensity
Dura,on
 Area under the Curve
Peak ,me
Peak plasma level
or Maximum drug
concentra,on
AUC amount of
drug absorbed
systemically
 Drug Concentra,ons in Tissues
Tissue biopsy
Verify malignancy
Blood flow?
Drug concentra,on?
 Drug Concentra,ons in Urine
and Feces
Indirect method
Feces expelled by biliary secre,on
Mass balance study account for the en9re
dose given to the pa,ent
Undissolved dosage form?
 Drug Concentra,ons in Saliva
Only the free drug diuses into the saliva
The saliva/plasma drug concentra,on ra,o is
less than 1 for many drugs.
mostly influenced by the pKa of the
drug and the pH of the saliva
Secondary indicator
 Forensic Drug Measurements
Forensic science applica,on of science to
personal injury, murder, and other legal
proceedings
Drug measurements in ,ssues obtained at
autopsy or in other bodily fluids such as saliva,
urine, and blood may be useful if a suspect or
vic,m has taken an overdose of a legal
medica,on, has been poisoned, or has been
using drugs of abuse
 Forensic Drug Measurements
Party/social drugs my be eliminated rapidly
Hair samples gas chromatography + mass
spectrometry past drug exposures
Heroine users hair samples has traces of
cocaine and 6-acetylmorphine metabolites
of diacetylmorphine
 Pharmacokine,c models
A model is a hypothesis using mathema,cal
terms to describe quan9ta9ve rela,onships
concisely
Define Pharmacokine9c model
 Pharmacokine,c models
1. Predict plasma, ,ssue, and urine drug levels
with any dosage regimen
2. Calculate the op,mum dosage regimen for
each pa,ent individually
3. Es,mate the possible accumula,on of drugs
and/or metabolites
4. Correlate drug concentra,ons with
pharmacologic or toxicologic ac,vity
 Pharmacokine,c models
5. Evaluate dierences in the rate or extent of
availability between formula,ons
(bioequivalence)
6. Describe how changes in physiology or disease
aect the absorp,on, distribu,on, or elimina,on
of the drug
7. Explain drug interac,ons
 Pharmacokine,c models
Empirical model simple
compartmental approach
Physiologically based model iden,fies actual
body spaces, region specific
Compartment model most useful
in pharmacokine,cs
 Compartment models
One compartment model what is the central
compartment?
Mammillary model most common
compartment model used in pharmacokine,cs
Catenary model consists of compartments
joined to one another like the compartments
of a train
Physiologic Pharmacokine,c Model
(Flow Model)
 Next Mee,ng
QUIZ #1
Prepare cross sec,onal paper and semi-log
paper