Inhibition of tacrine oral clearance by cimetidine

Clinical Pharmacology and Therapeutics
S T ForgueT M deVries

Abstract

Plasma tacrine, 1-hydroxytacrine, 2-hydroxytacrine, and 4-hydroxytacrine concentrations were measured in 12 healthy elderly subjects in this nonblinded two-period study to assess the effect of multiple doses of cimetidine on single-dose tacrine pharmacokinetics. Subjects received 40 mg tacrine (Cognex) alone and during multiple-dose cimetidine (300 mg four times a day) administration. Overall, tacrine and cimetidine were well tolerated by healthy elderly subjects. After coadministration of cimetidine with tacrine, plasma tacrine concentrations were approximately one-third higher than values after administration of tacrine alone; metabolite concentrations were also higher. Mean tacrine oral clearance was reduced by 30%; however, mean absorption rate and elimination half-life values were not affected by cimetidine. It was concluded that cimetidine inhibits first-pass hepatic extraction of tacrine by cytochrome P450 enzymes but has little effect on systemic drug clearance. Clinical considerations may dictate a reduction in tacrine dosage when tacrine is coadministered with cimetidine.

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Citations

May 19, 2009·Nanomedicine : Nanotechnology, Biology, and Medicine·Barnabas WilsonBhojraj Suresh
Nov 24, 2006·American Journal of Therapeutics·Malay K SamantaB Suresh
Apr 25, 2003·Drugs & Aging·Jennifer L Defilippi, M Lynn Crismon
Aug 7, 2002·Clinical Pharmacokinetics·Michael W JannGary W Small
Dec 5, 1998·British Journal of Clinical Pharmacology·P J TiseoL T Friedhoff

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