Interindividual variability in drug

Becquemont, L., Verstuyft, C. and Jaillon, P. (2006) Pharmacogenetics and interindividual variability in drug response cytochrome P-450 2C9 and coumarin anticoagulants. Bulletin de I Academie Nationale de Medecine, 190 (1), 37-49. discussion 50-3. 

These older antidepressants have a therapeutic range that is bound on the lower end by lack of efficacy and on the upper end by risk of serious toxicity. These drugs also have substantial interindividual variability in drug metabolism so that ineffective concentrations can develop in some patients on the usual dose and toxic concentrations can develop in others. For that reason, TDM is a standard of care issue when using TCAs to treat clinical depression ( 325). 

G.N. Levy, W.W. Weber, Interindividual Variability of A -Acetyltransferases in Man , in Interindividual Variability in Drug Metabolism in Man, eds. G. Pacifici, O. Pelkonen, Taylor and Francis, London, in press. 

Bertilsson L, Kalow W. Interethnic differences in drug disposition and effects. In Pacifici GM, Pelkonen O, eds. Interindividual Variability in Drug Metabolism in Humans. London Taylor Francis Ltd., 2001 15-75. 

Interspecies and interindividual variability in drug metabolism is influenced by both genetic and environmental factors. The basal rate of drug metabolism in a particular individual is determined primarily by genetic constitution, but also varies with age, gender, and environmental factors such as diet, disease states, and concurrent use of other drugs. 

Due to (1) the differential pharmacokinetics of the enantiomers of verapamil within each formulation, (2) differences in the rate of metabolism between various oral formulations, (3) large interindividual variability in drug effect (as measured by the PR interval), and (4) large interindividual variability in plasma verapamil concentration, the assessment of the bioequivalency of different verapamil formulations is not a trivial task (1,4,11). 

In general, genetic factors are estimated to account for 15-30% of interindividual differences in drug metabolism and response but for certain drugs or classes of drugs, genetic factors are of the utmost importance and can account for up to 95% of interindividual variability in drug disposition and effects [4]. 

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