How New Drugs Are Developed: Kinetics Evaluations
Pp. 163-222 (60)
Robert E. Smith
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, 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) match the individual compounds’ properties to
their physiological properties. This is a rational approach for predicting their
pharmaceutical properties  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.
Pharmacokinetics, toxicokinetics, “Cmax, Tmax, area under the curve,
AUC, bioavailability, clearance, volume of distribution”, the half-life for
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