Pharmacokinetics of intravenous and oral chlordesmethyldiazepam in patients on regular haemodialysis

Summary The pharmacokinetics of a single 2 mg IV dose of chlordesmethyldiazepam has been studied in 11 patients with renal failure on regular haemodialysis and in 11 age-matched healthy controls. The kinetics was also examined after a single 2 mg oral dose in 6 of the 11 renal failure patients.After intravenous administration the kinetics of total chlordesmethyldiazepam in renal patients and controls were the same. The unbound fraction of the drug in renal patients was higher (5.5%) than in controls (2.9%). Correction for differences in protein binding revealed a reduced apparent volume of distribution (47 vs. 140 l · kg^–1) and a reduced clearance (5.0 vs. 10.5 ml · min^–1 · kg^–1) in the patients. The systemic availability of oral chlordesmethyldiazepam was good (82%) despite a relatively slow absorption rate.