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.
Population pharmacokinetics
- 1. 牀 CLINICAL PHARMACOKINETICS AND THERAPEUTIC DRUG MONITORING 5.POPULATION PHARMACOKINETICS (PopPK) KrishnaShriram.D, 5th PharmD, The Erode College of Pharmacy DEFINITION: Populationpharmacokinetics(PopPK) is the study of variability in plasma drug concentrationsbetweenand withinpatient populationsreceivingtherapeuticdosesofa drug. Populationmodellingprovidesestimatesoftypical drug levelsand drug effects (PKor PK/PDparameters) inaspecificpopulation byidentifyingsourcesof variability (covariates) ina populationandthen quantifyingthe impact ofeach covariate through a modelling system. It ismost oftenappliedtothe clinical patientwhoisreceivingrelevantdosesof adrug of interest. PopPKexaminesthe relationshipof the demographic,genetic,pathophysiological, environmental,andotherdrug- relatedfactorsthatcontribute tothe variabilityobservedin safetyandefficacyof the drug.1 Both pharmacokineticandnon-pharmacokineticdatamaybe considered,includinggender, age,weight,creatinineclearance,andconcomitantdisease. Populationpharmacokineticscanbe usedto assist with therapeuticdrugmonitoring(TDM) and the principlesofdosage adjustments. FEATURES/PROCESS OF POPULATION PHARMACOKINETICS(PopPK): The PopPKapproach encompassessome of the followingfeatures(FDA Guidancefor Industry,1999) : a) Collectionofrelevantpharmacokinetic information inpatientsof the targetpopulationto be treatedwiththe drug, b) Identificationandmeasurementof variabilityduringdrug developmentandevaluation, c) Explanation ofvariability byidentifyingfactors(of demographic,pathophysiological, environmental,orconcomitantdrug-relatedoriginthatinfluencesthe pharmacokinetic behaviourof a drug),
- 2. d) Quantitative estimationofthe magnitude of the unexplainedvariability inthe patient population, e) Resolutionofthe issuescausing variability allowsforthe developmentof anoptimum dosingstrategy fora population,subgroup,orindividual patient. NEED FOR POPULATIONPKINETICS: One significantwaythatPKand PK/PDmodellingisusedisto helprefine the correct dosage. For eg : In drugsthat are mainlyeliminatedviaurinaryexcretion,the steady-state concentrations (CSS) are usually greaterinsubjectswith renal dysfunction comparedto those insubjectswithnormal renal function. Populationanalysis identifiesandquantitates thisdifference,assesseswhether this difference will alterthe dose-concentration-effectrelationship,andthen consequently determinesif dose adjustmentisneeded. A dosingregimenbasedonPopPKor PK/PDanalysisshouldbe includedinthe druglabel. REFERENCE: 1. AppliedBio-pharmaceutics&Pharmacokinetics,SeventhEdition,LeonShargel,PhD,RPh; Pg.No:714 2. https://blog.covance.com/2018/07/population-pk-pd-analysis/