SOP 13: Pharmacokinetic Data Analysis

Pharmacokinetic studies are an integrated part of the development program of a new drug. They are intended to define the time course of drug and major metabolite concentrations in plasma and other biological fluids in order to obtain information on absorption, distribution, metabolism, and elimination. In preclinical studies, pharmacokinetics (PK) is often used to interpret toxicological results. Animal toxicokinetic data can be used to guide dosage selection and escalation schemes in phase I dose tolerance studies. Pharmacokinetically guided dose escalation (PGDE) schemes are an example of the use of preclinical pharmacokinetic data for clinical dose finding in phase I studies. In clinical studies, PK is mainly required for dose finding and dose escalation studies. In phase II and phase III studies, the randomized concentration-controlled clinical trial should be regarded as alternative to the traditional dosecontrolled trial, particularly if interindividual variability of pharmacokinetic parameters is large. Population pharmacokinetic data analysis may reveal the influence of patientspecific factors on pharmacokinetic parameters providing valuable information for dosage individualization. For certain drugs, particularly those with a narrow therapeutic range, PK is used in clinical routine to adapt drug dosage to the individual patient (therapeutic drug monitoring). The statistical evaluation problem of pharmacokinetic data is defined by the tasks to describe the time course of the amount or concentration of the drug in the body and its compartments and to determine rate constants by which the drug reaches the target organs/tissues, by which the drug is activated or bound and by which it is eliminated from the body.