Chapter 4

How New Drugs Are Developed: Kinetics Evaluations

Robert E. Smith

Abstract

Pharmacokinetics is the science of determining how much of the drug reaches the target organs and how much is eliminated at different times after giving different doses, sometimes in various dosage forms. Toxicokinetics is similar to pharmacokinetics, except one is concerned with toxins, as opposed to medicinal drugs. However, when the dose of a medicinal drug becomes too high, it becomes toxic. So, toxicokinetics is much like pharmacokinetics, but at a higher dose. Important parameters include the maximum drug concentration, Cmax, the time it takes to reach maximum concentration, T<sub>max</sub>, the area under the curve, AUC, bioavailability, clearance, volume of distribution and the half-life [1] for clearance, t<sub>1/2</sub>. Physiological based pharmacokinetic models (PBPK) match the individual compounds’ properties to their physiological properties. This is a rational approach for predicting their pharmaceutical properties [1] in vivo. Drug metabolism occurs mostly in the liver and intestine. Phase I metabolism adds functional groups (-OH, -SH, -NH<sub>2</sub>, -COOH), while phase II involves biotransformation. Phase II enzymes add larger molecules and groups. Drugs can have multiple effects on the proteome, transcriptome, epigenome, metabolome and interactome of cells, tissues and organisms.

Total Pages: 163-222 (60)

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