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Review Article

Pharmacokinetics and drug metabolism in the elderly

Pages 67-76 | Received 29 Dec 2008, Accepted 30 Dec 2008, Published online: 01 May 2009
 

Abstract

Aging involves progressive impairments in the functional reserve of multiple organs, which might also affect drug metabolism and pharmacokinetics. In addition, the elderly population will develop multiple diseases and, consequently, often has to take several drugs. As the hepatic first-pass effect of highly cleared drugs could be reduced (due to decreases in liver mass and perfusion), the bioavailability of some drugs can be increased in the elderly. Significant changes in body composition occur with advancing age. Lipophilic drugs may have an increased volume of distribution (Vd) with a prolonged half-life, and water-soluble drugs tend to have a smaller Vd. In the elderly, hepatic drug clearance of some drugs can be reduced by up to 30% and CYP-mediated phase I reactions are more likely to be impaired than phase II metabolism, which is relatively preserved in the elderly. Concerning the most important CYP3A4 studies with human liver microsomes and clinical studies with the validated probe, midazolam, it is indicated that there are no significant differences in CYP3A4 activity between young and old populations. Finally, renal excretion is decreased (up to 50%) in about two thirds of elderly subjects, but confounding factors such as hypertension and coronary heart disease account also for a decline in kidney function. In conclusion, age-related physiological and pharmacokinetic changes as well as the presence of comorbidity and polypharmacy will complicate drug therapy in the elderly.

Acknowledgments

This work was supported by the Robert Bosch Foundation (Stuttgart, Germany). The secretarial assistance of Mrs. U. Hengemühle and some literature support by S. Shi, Ph.D. (HUST, Jongji Medical College, P. R. China) are highly appreciated.

Declaration of interest: The author reports no financial conflicts of interest. The author is responsible for the content and writing of this paper.

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