Clinical Pharmacology & Therapeutics · 1982 · 45 citations · 0 references
PharmacyPharmacokineticsPharmacologyDementiaDrug ClearanceRenal PharmacokineticsAge-related PharmacodynamicsAge-related Pharmacokinetic DifferencesAge-related PharmacokineticsPharmacokinetics In DementiaPharmacokinetics In Renal ImpairmentAge-related Drug EliminationAge-related Renal ClearanceClinical Pharmacology EvidenceDrug Metabolism In DementiaPharmacokinetics In AgingRenal Clearance DeclineRenal Elimination In AgingRenal Tubular Secretion
In 35 patients (ages 20 to 86 yr) receiving cimetidine therapeutically two serum samples and all urine formed in the interim were collected for analysis of cimetidine by high-pressure liquid chromatography and for creatinine. Cimetidine clearance decreased with age. The extrapolated 6-hr serum concentration of cimetidine per unit dose, after intravenous cimetidine, increased with age of the patients. The ratio of cimetidine clearance to creatinine clearance (Rc) averaged 4.8 +/- 2.0, indicating net tubular secretion for cimetidine. Rc seemed to be independent of age and decreased with increasing serum concentration of cimetidine, suggesting that secretion of cimetidine is a saturable process. There was only one case of dementia possibly due to cimetidine (with a drug level of 1.9 microgram/ml 6 hr after a dose) in a group of 13 patients without liver or kidney disease who had cimetidine levels above 1.25 microgram/ml. Thus, high cimetidine levels alone do not always induce dementia.