Title : Inhibition of tacrine oral clearance by cimetidine - Forgue_1996_Clin.Pharmacol.Ther_59_444
Author(s) : Forgue ST , Reece PA , Sedman AJ , deVries TM
Ref : Clinical Pharmacology & Therapeutics , 59 :444 , 1996
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.

PubMedSearch : Forgue_1996_Clin.Pharmacol.Ther_59_444
PubMedID: 8612390

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Citations formats

Forgue ST, Reece PA, Sedman AJ, deVries TM (1996)
Inhibition of tacrine oral clearance by cimetidine
Clinical Pharmacology & Therapeutics 59 :444

Forgue ST, Reece PA, Sedman AJ, deVries TM (1996)
Clinical Pharmacology & Therapeutics 59 :444