CPR - Chapter 36 (26 in cpr 8)
Clinical Pharmacokinetics and Therapeutic Drug monitoring
By Talha
I. Introduction
Therapeutic Drug Monitoring
Practice applied for small group of drugs (mostly with narrow therapeutic range) by maintaining
their serum-drug-conc. (SDC), within a patient’s specific therapeutic range, with other
measurements such as pharmacokinetics & pharmacodynamics, to individualize and optimize
patient response to drug therapy.
Serum drug conc. (SDC) is better predictor of patient’s response than the dosage of a
drug.
Drug levels assist to individualize patient’s dosage regimen.
Drug levels help in determining the cause of a change in patient’s pharmacokinetics.
Clinical Pharmacokinetics
Application of pharmacokinetic principles for the rational design of an individualized dosage
regimen.
II. Applying Clinical Pharmacokinetics in TDM
Practitioner’s Control = Amount of drug administration
Practitioner’s not Control = Pk & Pd variables (bioavailability, clearance, steady-state
SDC, pharmacological response).
Therapeutic range is not an absolute prediction because different patients response
differently to their SDC. For example, some patients will show effective response within
therapeutic range of drug where as some patients will show effective response at upper or
lower limits of therapeutic range of drug, etc.
Population Pharmacokinetic Value or Parameter = is mean or average value for a given
group of people. For example group of people with age 20-60 years and all with a defined
range of renal impairment.
Practitioners first assume the patient-specific ranges as average value of the population
and based on that they give a dosage regimen to a patient and then they observe if steady-
state range is achieved for that patient based on population value, then no need for further
adjustment of regimen. But if the practitioner’s predicted dosage regimen does not work
because of patient’s-specific different response, then practitioners try to change the dose
& frequency of the regimen to adjust it for that specific patient.
Timing for SDC Measurements =
, 1. Sometimes measured early in therapy to determine patient’s specific Pks
2. But mostly measure during ‘steady-state dosage interval’, to determine if SDC is
within therapeutic range. And it is important for the measurement of SDC to wait
after the drug administration, to let the maximum steady-state concentration.
3. Errors in timing of steady-state concentration for drugs with shorter half-life are big
concern than for drugs with longer half-life.
III. TDM Drugs and Common Characteristics
Table 1 – drugs which used for TDM, with population range
Drugs often monitored Using SDC
Table 2 – Drugs monitored by using SDC in specialty conditions
, IV. Equations (many complicated equations, I am not sure if they will come in FPGEE,
so I am not involving them right now, but please look into book yourself as well and
inform if something important is missing in this summary).
Linear Pk Drug Clearance = change in dose is proportional to same change in SDC. And half-
life and drug clearance remains constant as the drug-dose changes.
Estimating drug clearance (Cl) => Cl = V / 1.4 t1/2 (V is vol of distribution)
Non-Linear Pk Drug Clearance = change in dose leads to disproportional change in SDC. And
half-life and drug clearance change as the drug-dose changes. In Non-Linear-Drugs, increase in
dose leads = ↑ in half-life, ↓ in clearance and chance is steady-state conc. (Css).
Estimating drug clearance (Cl) => Cl = Vmax / Km + Cavg. ss (Vmax is maximum amount of
drug that can be eliminated per unit time, Km is drug serum conc. at which rate of elimination is
50% of Vmax)
VI. The Total Testing Process (TTP) Applied to TDM (This section is not present in
CPR 8 book, but it is in CPR 7 book as Section VI)
TDM involves both Laboratory (for analysis) and Clinicians (for SDC interpretation).
TTP involves all the steps of laboratory testing (beginning with clinical question to clinician-
patient interaction and until results of test on patient).
Components & Steps in TTP (4 component and 11 steps)
1. Preanalytical Component (4 steps)
A = clinical question, B = Selection of Test, C = Order of Test, D = Sample Collection
2. Analytical Component (3 steps)
A = Sample prep, B = Analysis Performance, C = Verification of Results
3. Postanalytical Component (4 steps)
A = Report of Results, B = Clinical Answer, C = Action, D = Effect on Patient
4. Regulatory Component = Its regulatory environment in which TDM is performed and all
above component affected by this.
TDM Contribution to TTP
1. TDM helps to improve many TTP steps such as: providing education, drug information,
interpretation of TDM results, sample collection, etc
2. Pharmacist greater involvement in TTP = assessing appropriateness of TDM, Timing of
sample collection, and Clinical interpretation of TDM results.
Clinical Pharmacokinetics and Therapeutic Drug monitoring
By Talha
I. Introduction
Therapeutic Drug Monitoring
Practice applied for small group of drugs (mostly with narrow therapeutic range) by maintaining
their serum-drug-conc. (SDC), within a patient’s specific therapeutic range, with other
measurements such as pharmacokinetics & pharmacodynamics, to individualize and optimize
patient response to drug therapy.
Serum drug conc. (SDC) is better predictor of patient’s response than the dosage of a
drug.
Drug levels assist to individualize patient’s dosage regimen.
Drug levels help in determining the cause of a change in patient’s pharmacokinetics.
Clinical Pharmacokinetics
Application of pharmacokinetic principles for the rational design of an individualized dosage
regimen.
II. Applying Clinical Pharmacokinetics in TDM
Practitioner’s Control = Amount of drug administration
Practitioner’s not Control = Pk & Pd variables (bioavailability, clearance, steady-state
SDC, pharmacological response).
Therapeutic range is not an absolute prediction because different patients response
differently to their SDC. For example, some patients will show effective response within
therapeutic range of drug where as some patients will show effective response at upper or
lower limits of therapeutic range of drug, etc.
Population Pharmacokinetic Value or Parameter = is mean or average value for a given
group of people. For example group of people with age 20-60 years and all with a defined
range of renal impairment.
Practitioners first assume the patient-specific ranges as average value of the population
and based on that they give a dosage regimen to a patient and then they observe if steady-
state range is achieved for that patient based on population value, then no need for further
adjustment of regimen. But if the practitioner’s predicted dosage regimen does not work
because of patient’s-specific different response, then practitioners try to change the dose
& frequency of the regimen to adjust it for that specific patient.
Timing for SDC Measurements =
, 1. Sometimes measured early in therapy to determine patient’s specific Pks
2. But mostly measure during ‘steady-state dosage interval’, to determine if SDC is
within therapeutic range. And it is important for the measurement of SDC to wait
after the drug administration, to let the maximum steady-state concentration.
3. Errors in timing of steady-state concentration for drugs with shorter half-life are big
concern than for drugs with longer half-life.
III. TDM Drugs and Common Characteristics
Table 1 – drugs which used for TDM, with population range
Drugs often monitored Using SDC
Table 2 – Drugs monitored by using SDC in specialty conditions
, IV. Equations (many complicated equations, I am not sure if they will come in FPGEE,
so I am not involving them right now, but please look into book yourself as well and
inform if something important is missing in this summary).
Linear Pk Drug Clearance = change in dose is proportional to same change in SDC. And half-
life and drug clearance remains constant as the drug-dose changes.
Estimating drug clearance (Cl) => Cl = V / 1.4 t1/2 (V is vol of distribution)
Non-Linear Pk Drug Clearance = change in dose leads to disproportional change in SDC. And
half-life and drug clearance change as the drug-dose changes. In Non-Linear-Drugs, increase in
dose leads = ↑ in half-life, ↓ in clearance and chance is steady-state conc. (Css).
Estimating drug clearance (Cl) => Cl = Vmax / Km + Cavg. ss (Vmax is maximum amount of
drug that can be eliminated per unit time, Km is drug serum conc. at which rate of elimination is
50% of Vmax)
VI. The Total Testing Process (TTP) Applied to TDM (This section is not present in
CPR 8 book, but it is in CPR 7 book as Section VI)
TDM involves both Laboratory (for analysis) and Clinicians (for SDC interpretation).
TTP involves all the steps of laboratory testing (beginning with clinical question to clinician-
patient interaction and until results of test on patient).
Components & Steps in TTP (4 component and 11 steps)
1. Preanalytical Component (4 steps)
A = clinical question, B = Selection of Test, C = Order of Test, D = Sample Collection
2. Analytical Component (3 steps)
A = Sample prep, B = Analysis Performance, C = Verification of Results
3. Postanalytical Component (4 steps)
A = Report of Results, B = Clinical Answer, C = Action, D = Effect on Patient
4. Regulatory Component = Its regulatory environment in which TDM is performed and all
above component affected by this.
TDM Contribution to TTP
1. TDM helps to improve many TTP steps such as: providing education, drug information,
interpretation of TDM results, sample collection, etc
2. Pharmacist greater involvement in TTP = assessing appropriateness of TDM, Timing of
sample collection, and Clinical interpretation of TDM results.
