Age, disease, and cimetidine disposition in healthy subjects and chronically ill patients

Publisher Website
Google Scholar
Abstract
The antihistamine cimetidine induces reversible dose-related CNS toxicity. Trough serum concentrations and the development of CNS toxicity correlate. Cimetidine kinetics were compared in 12 healthy subjects and 31 patients. Six of the latter had normal renal and liver function, 5 had renal disease only, 12 had liver disease only and 8 had both renal and liver disease. Postmortem tissue distribution was assessed in 11 patients, and expressed as tissue:serum ratio. Average cimetidine total clearance (ClB) in milliliters per minute for each group was as follows: patients with renal and liver disease (182 .+-. 105), renal disease only (193 .+-. 24), liver disease only (463 .+-. 145), normal patients (510 .+-. 93), and healthy subjects (583 .+-. 140). Renal function was the major determinant of ClB, and the relationship was described by ClB = 4.2(CCr) + 140, r = 0.87, where CCr is creatinine clearance. Cimetidine clearance was affected little by age. Tissue:serum ratios from highest to lowest were kidney > stomach > liver > bone > brain > fat. Central and steady-state distribution volumes were not influenced by age or disease. There was enhanced CNS penetration in liver disease patients; their CSF:serum ratio was twice the normal. The kinetic studies identify patient characteristics likely to result in elevated blood levels and suggest that the greatest risk of CNS toxicity is in those with liver disease.

This publication has 1 reference indexed in Scilit: