Drug Metabolism and Pharmacokinetics in Drug Product Development

Abstract

The course illustrates the eminent role Drug Metabolism and Pharmacokinetics (DMPK) play all along the Research & Development Value Chain in the pharmaceutical industry: DMPK data guide lead compound optimization as well as formulation and clinical developments. Furthermore, the importance of DMPK for the comparison of generic and biosimilar drug products is elaborated.

Objective

• Students can explain compound selection and lead optimization with respect to biopharmaceutic and pharmacokinetic drug properties, including biological, physicochemical and computational strategies; the properties include, e.g., gastrointestinal absorption, protein binding, brain permeation, and metabolic profiling. • Students can apply biopharmaceutic and pharmacokinetic concepts in the evaluation of the biopharmaceutic quality of dosage forms, the design and optimization of controlled-release dosage forms, and the drug product registration process. • Students can understand and discuss the principles of biopharmaceutic characterization and evaluation of candidate drugs and dosage forms; they can integrate their knowledge of computational, in vitro, in situ, and in vivo tools in drug and dosage form development and evaluation processes.

Content

DMPK is one of the three core team functions of the lead optimization projects besides Pharmacology and Medicinal Chemistry that together optimize, select and profile drug development candidates. Another key contribution is the prediction of the PK behavior of drug candidates in animals and in humans, and the estimation of the human efficacious dose and the therapeutic range in patients. This is of relevance to any discipline working along the R&D value chain in the pharmaceutical industry which is why DMPK plays such a central role in drug discovery and development. Similarly, without proper biopharmaceutic characterization of the formulated drugs, i.e. the finished dosage form, formulation development would be inefficient and result in poorly performing drug products in humans. The following topics are addressed: • Biopharmaceutics, Metabolism and Pharmacokinetics in Industrial Drug Discovery and Drug Product Development – an overview; • Early drug candidate pharmaceutic and biopharmaceutic profiling – in vitro tools including physiological barriers to drug input, distribution and excretion and transporter mediated processes and in silico tools; • DMPK support in drug discovery including PK analysis in drug discovery, physiologically-based pharmacokinetic (PBPK) modeling, prediction of PK in animals and human and simulation and modelling in Drug Discovery and Development, Allometric scaling: From animals to man; Pharmacokinetics as a predictor of drug effect: PK/PD relationships and models; • Biopharmaceutic properties and molecular structure optimization including in silico predictions of biopharmaceutic properties from molecular structure (e.g. clogP, ADMET predictor), BCS, Rule of five, BDDCS; • Biopharmaceutic drug product comparison, including bioavailability and bioequivalence, biorelevant in vitro dissolution methods, in vitro / In vivo correlation, biowaivers; • Hands-on computer demonstrations and exercises (GastroPlus®, Deconvolution, Wagner-Nelson, Loo-Riegelman, Mean time analysis, DDDPlus®. Analysis of given problem sets; • Computer demonstrations (ADMET predictor®, clogP and Modern Biopharmaceutics CD). The seminars consist of (i) interactive lectures, ii) individual hands-on exercises, and (iii) simulated project team meetings that together illustrate the variety of contributions and the strong impact that the biopharmaceutic function is making on the research and early/late development phase, with practical examples, case studies and anecdotes to bring basic science to life.

Resources