Inhibition of tacrine oral clearance by cimetidine

Clin Pharmacol Ther. 1996 Apr;59(4):444-9. doi: 10.1016/S0009-9236(96)90114-9.


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.

Publication types

  • Clinical Trial
  • Controlled Clinical Trial

MeSH terms

  • Aged
  • Analysis of Variance
  • Cholinesterase Inhibitors / blood
  • Cholinesterase Inhibitors / pharmacokinetics*
  • Cimetidine / pharmacology*
  • Drug Interactions
  • Female
  • Half-Life
  • Histamine H2 Antagonists / pharmacology*
  • Humans
  • Male
  • Middle Aged
  • Tacrine / blood
  • Tacrine / pharmacokinetics*


  • Cholinesterase Inhibitors
  • Histamine H2 Antagonists
  • Tacrine
  • Cimetidine