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The aim of TDM is to provide maximum beneficial effects of drugs, and minimum risks of toxicities with added advantages of pharmacoeconomics
Pharmacokinetic studies are based on the concept that Pharmacologic response of a drug is closely related to concentration of drug at the receptor site (or site of action )
Toxic level
Maximum Therapeutic Concentration
Plasma conc.
Therapeutic Range
Minimum Therapeutic Concentration
concentration
Individual patient response often plays an important role in the determination of therapeutic and toxic concentration of drug in
the plasma
In most scientific studies large difference have been reported in individual patients to treatment with given drug
Therapeutic drug monitoring can be applied for 1. Obtaining maximum beneficial outcome of drug therapy 2. Attaining the required therapeutic concentration of the drug within least time 3. Maintaining the concentration of the drug within the therapeutic range such that no toxic effects are produced 4. Regulation of drug therapy by monitoring the concentration of drug plasma and its pharmacological response 5. Providing medical advantage by reducing the chances of drug toxicity. 6. Providing economic convenience to patients by shortening their stay in the hospital
Objectives Of TDM
7. Monitoring the factors like disease state, patients characteristics, drug interactions in order to reduce variability between individuals.
11. In a poisoned patient, the type and extent of poising can be identified immediately. And also helps in monitoring the amount of antidote & its efficiency
been checked
A great cost reduction is obtain when the laboratory performing the TDM
has appropriate consultation service A number of studies on cost effectiveness have demonstrated that TDM improves patient outcome by reducing the rate of drug induced toxicity, improving the success of treatment and decreasing morbidity
4. Disease diagnosed as
5. Details of treatment he/she is undergoing 6. Patient history for allergies or about previous medication 7. Time and date of administration 8. Duration of stay at hospital 9. Functional status of organs like liver, kidney presently or previous reports regarding the same 10. Reasons for TDM i. Poor response for drugs
Actual Value
t1/2
Safety range
Steady State
Remarks
Digoxin
Mg/kg
Od Bid Tid
hrs
Mg/l
Functions of TDM
1. 2. 3. 4. 5. 6. 7. 8. 9. Selection of drug Design dosage regimen Evaluate patient response Determine need for measuring serum drug concentration Assay for drug Pharmacokinetic evaluation of drug levels Readjust dosage regimen Monitor serum drug concentration Recommend special requirements
Drug Factors :bioavailability & biopharmaceutics pharmacokinetics, drug interactions, receptor sensitivity rapid and slow metabolism
5.Patient compliance
Institutionalized patients Ambulatory patients
factors that may effect include
Cost of the medication Complicated instructions Multiple daily doses Difficulty in swallowing ADR
Patient compliance
o
o o o o
Slow elimination
Increased plasma protein binding Smaller than anticipated apparent volume of distribution Deteriorating renal/ hepatic function Drug interaction due to inhibition of elimination
Serum concentration correct but patient does not respond to therapy Altered receptor sensitivity Drug interaction at receptor site Changing hepatic blood flow
10.Dosage adjustment
From SDC data and patient observations the clinician or pharmacokineticist may recommend an adjustment in dosage If sufficient data is not available pharmacokineticist can derive a new dosage regimen based on available data or pharmacokinetic parameters in the literature that are based on AVG population data
12.Special recommendation
If the patients are not responding to the therapy evaluate patient compliance and instructions
Several methods may be used to design a dosage regimen Initial dosage of drug is estimated using AVG population pharmacokinetic parameters obtained from the literature
Individualized Dosage Regimens: This is the most accurate approach to dosage regimen design based on the pharmacokinetics of the drug
Adaptive model: This method uses patient variables such as weight, age, sex,
body surface area and known patient Pathophysiology such as renal disease, as well as the known population AVG pharmacokinetic parameters of the drug In this case the calculation of dosage regimen takes into consideration any changing Pathophysiology of the patient and attempts to adapt or modify the dosage regimen according to the needs of the patient
TDM Protocol
Clinical condition requiring TDM Sample collected at appropriate time store and estimate drug concentration
Good response continue the drug not responding Review the case check for compliance Yes TDM test Sub-therapeutic increase the dose No Educate patient & family therapeutic change over to second drug or add another drug toxicity TDM test adjust the dose
Repeat the TDM good response no response continue the same drug change to second drug or add another drug
Check adherence
Check adherence
If adherent consider small dose increase if result is at lower end of range Alternatively consider change of therapy
Consider other explanation for patient signs and symptoms lab, errors
Consider other explanation for patient signs and symptoms if results are at upper end lower the dose
9. Pharmacokinetic profiling
Analyticala aspects of TDM procedure For an efficient TDM thoroughly developed analytical
is necessary for estimation of SDC biological sample
The method should meet the specifications of handling of The method selected should have sensitivity, specificity linearity
1.Specificity:
There should be evidence that method is specific for drug There is no interference between the drug metabolites of the drug & endogenous or exogenous substance
compounds
2.Sensitivity:
This is the minimum detectable level or concentration
3.Precision:
This the measurement of variability or reproducibility of the data usually obtained by replication of various drug
4.Accuracy;
concentration.
6.Stability:
Standard drug concentration should be maintained under
7.Ruggedness:
This is the degree of reproducibility of the test results.
Therapeutic drug monitoring refers to the measurement of drug concentration in biological fluids with the purpose of optimizing a patients drug therapy
The aim of TDM is to provide maximum beneficial effects of drugs, and minimum risks of toxicities with added advantages of pharmacoeconomics
Therapeutic drug monitoring refers to the measurement of drug concentration in biological fluids with the purpose of optimizing a patients drug therapy
The aim of TDM is to provide maximum beneficial effects of drugs, and minimum risks of toxicities with added advantages of pharmacoeconomics
Pharmacokinetic studies are based on the concept that Pharmacologic response of a drug is closely related to concentration of drug at the receptor site (or site of action )
Toxic level
Maximum Therapeutic Concentration
Plasma conc.
Therapeutic Range
Minimum Therapeutic Concentration
concentration
Individual patient response often plays an important role in the determination of therapeutic and toxic concentration of drug in
the plasma
In most scientific studies large difference have been reported in individual patients to treatment with given drug
Therapeutic drug monitoring can be applied for 1. Obtaining maximum beneficial outcome of drug therapy 2. Attaining the required therapeutic concentration of the drug within least time 3. Maintaining the concentration of the drug within the therapeutic range such that no toxic effects are produced 4. Regulation of drug therapy by monitoring the concentration of drug plasma and its pharmacological response 5. Providing medical advantage by reducing the chances of drug toxicity. 6. Providing economic convenience to patients by shortening their stay in the hospital
Objectives Of TDM
7. Monitoring the factors like disease state, patients characteristics, drug interactions in order to reduce variability between individuals.
11. In a poisoned patient, the type and extent of poising can be identified immediately. And also helps in monitoring the amount of antidote & its efficiency
been checked
A great cost reduction is obtain when the laboratory performing the TDM
has appropriate consultation service A number of studies on cost effectiveness have demonstrated that TDM improves patient outcome by reducing the rate of drug induced toxicity, improving the success of treatment and decreasing morbidity
4. Disease diagnosed as
5. Details of treatment he/she is undergoing 6. Patient history for allergies or about previous medication 7. Time and date of administration 8. Duration of stay at hospital 9. Functional status of organs like liver, kidney presently or previous reports regarding the same 10. Reasons for TDM i. Poor response for drugs
Actual Value
t1/2
Safety range
Steady State
Remarks
Digoxin
Mg/kg
Od Bid Tid
hrs
Mg/l
Functions of TDM
1. 2. 3. 4. 5. 6. 7. 8. 9. Selection of drug Design dosage regimen Evaluate patient response Determine need for measuring serum drug concentration Assay for drug Pharmacokinetic evaluation of drug levels Readjust dosage regimen Monitor serum drug concentration Recommend special requirements
Drug Factors :bioavailability & biopharmaceutics pharmacokinetics, drug interactions, receptor sensitivity rapid and slow metabolism
5.Patient compliance
Institutionalized patients Ambulatory patients
factors that may effect include
Cost of the medication Complicated instructions Multiple daily doses Difficulty in swallowing ADR
Patient compliance
o
o o o o
Slow elimination
Increased plasma protein binding Smaller than anticipated apparent volume of distribution Deteriorating renal/ hepatic function Drug interaction due to inhibition of elimination
Serum concentration correct but patient does not respond to therapy Altered receptor sensitivity Drug interaction at receptor site Changing hepatic blood flow
10.Dosage adjustment
From SDC data and patient observations the clinician or pharmacokineticist may recommend an adjustment in dosage If sufficient data is not available pharmacokineticist can derive a new dosage regimen based on available data or pharmacokinetic parameters in the literature that are based on AVG population data
12.Special recommendation
If the patients are not responding to the therapy evaluate patient compliance and instructions
Several methods may be used to design a dosage regimen Initial dosage of drug is estimated using AVG population pharmacokinetic parameters obtained from the literature
Individualized Dosage Regimens: This is the most accurate approach to dosage regimen design based on the pharmacokinetics of the drug
Adaptive model: This method uses patient variables such as weight, age, sex,
body surface area and known patient Pathophysiology such as renal disease, as well as the known population AVG pharmacokinetic parameters of the drug In this case the calculation of dosage regimen takes into consideration any changing Pathophysiology of the patient and attempts to adapt or modify the dosage regimen according to the needs of the patient
TDM Protocol
Clinical condition requiring TDM Sample collected at appropriate time store and estimate drug concentration
Good response continue the drug not responding Review the case check for compliance Yes TDM test Sub-therapeutic increase the dose No Educate patient & family therapeutic change over to second drug or add another drug toxicity TDM test adjust the dose
Repeat the TDM good response no response continue the same drug change to second drug or add another drug
Check adherence
Check adherence
If adherent consider small dose increase if result is at lower end of range Alternatively consider change of therapy
Consider other explanation for patient signs and symptoms lab, errors
Consider other explanation for patient signs and symptoms if results are at upper end lower the dose
9. Pharmacokinetic profiling
Analyticala aspects of TDM procedure For an efficient TDM thoroughly developed analytical
is necessary for estimation of SDC biological sample
The method should meet the specifications of handling of The method selected should have sensitivity, specificity linearity
1.Specificity:
There should be evidence that method is specific for drug There is no interference between the drug metabolites of the drug & endogenous or exogenous substance In addition the internal standard should be resolved completely and also demonstrate no interference with other compounds
2.Sensitivity:
This is the minimum detectable level or concentration
3.Precision:
This the measurement of variability or reproducibility of the data usually obtained by replication of various drug
4.Accuracy;
concentration.
6.Stability:
Standard drug concentration should be maintained under
7.Ruggedness:
This is the degree of reproducibility of the test results.