Population pharmacokinetics

Population pharmacokinetics (PopPK) is the study of variability in plasma drug concentrations between and within patient populations receiving therapeutic doses of a drug.
• Population modelling provides estimates of typical drug levels and drug effects (PK or PK/PD parameters) in a specific population by identifying sources of variability (covariates) in a population and then quantifying the impact of each covariate through a modelling system.
• Population pharmacokinetics can be used to assist with therapeutic drug monitoring (TDM) and the principles of dosage adjustments.
• Population analysis identifies and quantitates this difference, assesses whether this difference will alter the dose-concentration-effect relationship, and then consequently determines if dose adjustment is needed.
• A dosing regimen based on Pop PK or PK/PD analysis should be included in the drug label.

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CLINICAL PHARMACOKINETICS AND THERAPEUTIC DRUG MONITORING
5.POPULATION PHARMACOKINETICS (PopPK)
Krishna Shriram. D,
5
th
PharmD,
The Erode College of Pharmacy

DEFINITION:
 Population pharmacokinetics (PopPK) is the study of variability in plasma drug
concentrations between and within patient populations receiving therapeutic doses of a
drug.

 Population modelling provides estimates of typical drug levels and drug effects (PK or
PK/PD parameters) in a specific population by identifying sources of variability (covariates)
in a population and then quantifying the impact of each covariate through a modelling
system.

 It is most often applied to the clinical patient who is receiving relevant doses of a drug of
interest.

 PopPK examines the relationship of the demographic, genetic, pathophysiological,
environmental, and other drug- related factors that contribute to the variability observed in
safety and efficacy of the drug.
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 Both pharmacokinetic and non-pharmacokinetic data may be considered, including gender,
age, weight, creatinine clearance, and concomitant disease.

 Population pharmacokinetics can be used to assist with therapeutic drug monitoring (TDM)
and the principles of dosage adjustments.

FEATURES/PROCESS OF POPULATION PHARMACOKINETICS (PopPK):
The PopPK approach encompasses some of the following features (FDA Guidance for
Industry, 1999) :

a) Collection of relevant pharmacokinetic information in patients of the target population to
be treated with the drug,
b) Identification and measurement of variability during drug development and evaluation,
c) Explanation of variability by identifying factors (of demographic, pathophysiological,
environmental, or concomitant drug-related origin that influences the pharmacokinetic
behaviour of a drug),

2. d) Quantitative estimation of the magnitude of the unexplained variability in the patient
population,
e) Resolution of the issues causing variability – allows for the development of an optimum
dosing strategy for a population, subgroup, or individual patient.


NEED FOR POPULATION P’KINETICS:
 One significant way that PK and PK/PD modelling is used is to help refine the correct
dosage.

 For eg :
In drugs that are mainly eliminated via urinary excretion, the steady-state
concentrations (CSS) are usually greater in subjects with renal dysfunction compared to
those in subjects with normal renal function.

 Population analysis identifies and quantitates this difference, assesses whether this
difference will alter the dose-concentration-effect relationship, and then consequently
determines if dose adjustment is needed.
 A dosing regimen based on Pop PK or PK/PD analysis should be included in the drug label.



REFERENCE:

1. Applied Bio-pharmaceutics & Pharmacokinetics, Seventh Edition, Leon Shargel, PhD, RPh;
Pg.No: 714
2. https://blog.covance.com/2018/07/population-pk-pd-analysis/