Clorazepate Dipotassium and Diazepam in Renal Insufficiency: Serum Concentrations and Protein Binding of Diazepam and Desmethyldiazepam
作者:
Hermann R. Ochs,
Hans Werner Rauh,
David J. Greenblatt,
Hans J. Kaschell,
期刊:
Nephron
(Karger Available online 1984)
卷期:
Volume 37,
issue 2
页码: 100-104
ISSN:1660-8151
年代: 1984
DOI:10.1159/000183222
出版商: S. Karger AG
关键词: Diazepam;Renal insufficiency;Protein binding;Desmethyldiazepam;Clorazepate dipotassium
数据来源: Karger
摘要:
5 patients with chronic renal failure on maintenance hemodialysis and 5 healthy matched controls received single 20-mg intravenous doses of clorazepate dipotassium. Clearance of pharmacologically active unbound desmethyldiazepam was reduced in renal failure patients as opposed to controls, and free fraction in serum was greater. Since desmethyldiazepam distribution was reduced in renal patients, elimination half-life was actually shorter than in controls (36 vs. 57 h). In 10 dialysis patients receiving chronic diazepam treatment (5–15 mg/day), steady-state concentrations of diazepam (56 ng/ml) and desmethyldiazepam (77 ng/ml) were significantly lower than in age- and weight-matched controls receiving similar doses (189 and 216 ng/ml, respectively). However after correction for the higher free fractions of both compounds in renal patients as opposed to controls, steady-state concentrations of unbound drug were found to be similar between groups. Interpretation of kinetic variables and steady-state serum concentrations of extensively protein-bound drugs requires consideration of alterations in protein binding that may occur in disease state
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