Medicinal Chemistry - Fusion of Traditional and Western Medicine

Volume: 1

How New Drugs are Developed: Kinetics Evaluations

Author(s): Robert E. Smith

Pp: 117-131 (15)

DOI: 10.2174/9781608051496113010005

* (Excluding Mailing and Handling)

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 the earlier one is concerned with toxins, while the latter with 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 Cmax, the time it takes to reach maximum concentration, Tmax, the area under the curve, AUC, bioavailability, clearance, volume of distribution and the half-life for clearance, t1/2. Physiological based pharmacokinetic models (PBPK) involve a natural way of integrating the individual compound property to physiological properties, providing a rational approach to predict drug like behavior in vivo. Drug metabolism occurs mostly in the liver and intestine. Phase I metabolism adds functional groups (-OH,-SH,-NH2,-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.


Keywords: Pharmacokinetics, toxicokinetics, Cmax, Tmax, area under the curve, AUC, bioavailability, clearance, volume of distribution, the half-life for clearance, t1/2.

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