Pharmacokinetics drug concentration monitoring

Therapeutic drug monitoring (TDM) or applied pharmacokinetics is the use of serum drug concentrations to optimize therapy.28,36,37 Non-AIDS patients with drug-susceptible TB... 

Therapeutic drug monitoring The process of using drug concentrations, pharmacokinetic principles, and pharmacodynamic criteria to optimize drug therapy in individual patients. 

This information may affect selection criteria for the study population and the choice of tests in addition to routine safety monitoring, and will certainly determine the starting dose, range of doses, maximum exposure and dose increments to be studied. Pharmacokinetics in man may be quite different from those in animal species so that plasma and, if possible, tissue concentrations are generally more important than dose. One exception to this may be hepatotox-icity resulting from exposure of the liver to portal blood drug concentrations, when the oral dose administered to the animals may be more relevant than the systemic plasma concentrations, which reflect first-pass metabolism as well as absorption. 

MacKichan JJ (2006) Influence of protein binding and use of unbound (free) drug concentrations. In Burton ME, Shaw LM, Schentag JJ, et al., eds. Applied Pharmacokinetics and Pharmacodynamics. Principles of Therapeutic Drug Monitoring, 4th edn, pp 82-120. Baltimore Lippincott Williams Wilkins. 

The major route of elimination is hepatic metabolism. The variability in the metabolism and pharmacokinetics in neonates, infants and children necessitates monitoring of drug concentrations in the plasma, particularly when it is co-administered with phenytoin, phenobarbital or rifampin. 

Many biochemistry laboratories no longer undertake routine measurement of the plasma concentration for most anticonvulsant drugs because plasma concentrations are insufficiently stable to serve as a useful guide to change of dose. The exception is phenytoin, where a small increase in dose may lead to a disproportionate rise in the plasma drug concentration (see zero-order pharmacokinetics, p. 99) and plasma monitoring is essential. With other drugs the dose is increased to the maximum tolerated level and, if seizures continue, it is replaced by another. 

Figure 33-10 Dose-response curves. L/ne A illustrates the linear relationship between serum drug concentration and total daily dose of a drug that displays first-order kinetics typical of most drugs. Line B illustrates the dose-response relationship for a drug that displays capacity-limited kinetics because of a saturable enzyme or transport mechanism in this situation, serum concentration becomes independent of total daily dose, and the relationship of drug concentration to dose becomes nonlinear. (Modified from Pippenger CE. Practical pharmacokinetic appiications. Syvo Monitor, Son Jose Syva Co, January, i 979 1-4.)...

For every patient with a serum drug concentration ordered, the primary pharmacist writes a Clinical Pharmacokinetics note in the progress notes section of the patient s chart within 24 hours for normal or subthe-rapeutic concentrations. For supratherapeutic drug concentrations, the medical team is notified immediately if clinically warranted and a chart note written within 12 hours after the concentration was reported. The chart note contains all relevant patient information and pharmacokinetic parameters necessary to provide dosing and monitoring recommendations. ... 

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