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Population Analyses of Atorvastatin Clearance in Patients Living in the Community and in Nursing Homes
Clinical Pharmacology & Therapeutics, 07/02/09
Schwartz JB et al. - The time of dose administration had a strong influence on Ka; the factors found to slow CL/F were coadministration of CYP3A inhibitors and advancing age—the latter factor was relevant only in the men, not in the women.
JB Schwartz, 07/02/09
| This investigation used atorvastatin as a probe of influences on oral clearance rates of the most common hepatic and intestinal cytochrome P450 enzyme (CYP3a) CYP3A in patients, including the very old. As in our prior studies of nifedipine, verapamil, amlopidipine, and erythromycin, sex and the administration of enzyme inhibitors or inducers were the strongest determinants of drug clearance. Increasing age over 60 years was not a factor in women who comprise the majority of the older population, but was detected in some of the groups of men. This helps to explain the apparent discrepancies in results of investigations of age-related changes in CYP3A clearance since men have been the majority of subjects in studies of healthy aging and early clinical trials of agents, while women comprise the majority of patients at older ages. It is also key in showing that environmental factors such as co-medications have major effects and need to be considered when prescribing for older patients. |
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