Inhibition of tacrine oral clearance by cimetidine

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.

Caffeine based measures of CYP1A2 activity correlate with oral clearance of tacrine in patients with Alzheimer's disease

“…CYP1A2. The importance of CYP1A2 in the elimination of both tacrine and 1‐OH tacrine would also account for why treatment with cimetidine has been shown to cause increases in the AUC of 1‐OH tacrine in addition to increases in the AUC of parent tacrine [40]. It seems reasonable to assume that competition between tacrine and its metabolites for CYP1A2 metabolism may complicate the relationship between tacrine clearance and CYP1A2 activity.…”

Chitosan nanoparticles as a new delivery system for the anti-Alzheimer drug tacrine

“…45 The oral clearance of tacrine was inhibited by 30% after administration with cimetidine. 46 In the present work we studied chitosan nanoparticles as a new delivery system for the anti-Alzheimer drug tacrine and the effect of Polysorbate 80 coating on its biodistribution studies on rats.…”

Effects of the cimetidine on the biliary excretion of rosebengal in rats

“…Studies on the effect of cimetidine after a single dose showed a clear relationship between blood concentration and extent of inhibition of basal gastric acid 7 . When cimetidine was co-administered with other drugs clinically significant drug-drug interactions were observed and reported 8,9 . The excretion rate of cimetidine may invariably determine the duration of action.…”