Biomaterial Database

Inhibition of tacrine oral clearance by cimetidine. 1996

S T Forgue, and P A Reece, and A J Sedman, and T M deVries

Pharmacokinetics/Drug Metabolism Department, Parke-Davis Pharmaceutical Research Division, Warner-Lambert Company, Ann Arbor, MI 48105, USA.

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.

UI	MeSH Term	Description	Entries
D008297	Male		Males
D008875	Middle Aged	An adult aged 45 - 64 years.	Middle Age
D002800	Cholinesterase Inhibitors	Drugs that inhibit cholinesterases. The neurotransmitter ACETYLCHOLINE is rapidly hydrolyzed, and thereby inactivated, by cholinesterases. When cholinesterases are inhibited, the action of endogenously released acetylcholine at cholinergic synapses is potentiated. Cholinesterase inhibitors are widely used clinically for their potentiation of cholinergic inputs to the gastrointestinal tract and urinary bladder, the eye, and skeletal muscles; they are also used for their effects on the heart and the central nervous system.	Acetylcholinesterase Inhibitor,Acetylcholinesterase Inhibitors,Anti-Cholinesterase,Anticholinesterase,Anticholinesterase Agent,Anticholinesterase Agents,Anticholinesterase Drug,Cholinesterase Inhibitor,Anti-Cholinesterases,Anticholinesterase Drugs,Anticholinesterases,Cholinesterase Inhibitors, Irreversible,Cholinesterase Inhibitors, Reversible,Agent, Anticholinesterase,Agents, Anticholinesterase,Anti Cholinesterase,Anti Cholinesterases,Drug, Anticholinesterase,Drugs, Anticholinesterase,Inhibitor, Acetylcholinesterase,Inhibitor, Cholinesterase,Inhibitors, Acetylcholinesterase,Inhibitors, Cholinesterase,Inhibitors, Irreversible Cholinesterase,Inhibitors, Reversible Cholinesterase,Irreversible Cholinesterase Inhibitors,Reversible Cholinesterase Inhibitors
D002927	Cimetidine	A histamine congener, it competitively inhibits HISTAMINE binding to HISTAMINE H2 RECEPTORS. Cimetidine has a range of pharmacological actions. It inhibits GASTRIC ACID secretion, as well as PEPSIN and GASTRIN output.	Altramet,Biomet,Biomet400,Cimetidine HCl,Cimetidine Hydrochloride,Eureceptor,Histodil,N-Cyano-N'-methyl-N''-(2-(((5-methyl-1H-imidazol-4-yl)methyl)thio)ethyl)guanidine,SK&F-92334,SKF-92334,Tagamet,HCl, Cimetidine,Hydrochloride, Cimetidine,SK&F 92334,SK&F92334,SKF 92334,SKF92334
D004347	Drug Interactions	The action of a drug that may affect the activity, metabolism, or toxicity of another drug.	Drug Interaction,Interaction, Drug,Interactions, Drug
D005260	Female		Females
D006207	Half-Life	The time it takes for a substance (drug, radioactive nuclide, or other) to lose half of its pharmacologic, physiologic, or radiologic activity.	Halflife,Half Life,Half-Lifes,Halflifes
D006635	Histamine H2 Antagonists	Drugs that selectively bind to but do not activate histamine H2 receptors, thereby blocking the actions of histamine. Their clinically most important action is the inhibition of acid secretion in the treatment of gastrointestinal ulcers. Smooth muscle may also be affected. Some drugs in this class have strong effects in the central nervous system, but these actions are not well understood.	Antihistaminics, H2,H2 Receptor Blockader,Histamine H2 Antagonist,Histamine H2 Blocker,Histamine H2 Receptor Antagonist,Histamine H2 Receptor Antagonists,Histamine H2 Receptor Blockader,Histamine H2 Receptor Blockaders,Antagonists, Histamine H2,Blockaders, Histamine H2 Receptor,H2 Receptor Blockaders,Histamine H2 Blockers,Receptor Antagonists, Histamine H2,Receptor Blockaders, H2,Antagonist, Histamine H2,Blockader, H2 Receptor,Blockaders, H2 Receptor,Blocker, Histamine H2,Blockers, Histamine H2,H2 Antagonist, Histamine,H2 Antagonists, Histamine,H2 Antihistaminics,H2 Blocker, Histamine,H2 Blockers, Histamine,Receptor Blockader, H2
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000368	Aged	A person 65 years of age or older. For a person older than 79 years, AGED, 80 AND OVER is available.	Elderly