Effects of uremia and hemodialysis on lormetazepam disposition

Autor: Kessel M, Ursula Lerche, Michael Huempel, Dieter Kampf
Rok vydání: 1981
Předmět:
Zdroj: Clinical pharmacology and therapeutics. 30(1)
ISSN: 0009-9236
Popis: Lormetazepam kinetics were studied after a single 1-mg dose orally in five patients with terminal renal failure in the dialysis-free interval and during 4- to 5-hr hemodialysis. Lormetazepam and lormetazepam glucuronide concentrations were determined by a specific and sensitive radioimmunoassay. Results were compared with data on six healthy subjects. In renal insufficiency, lormetazepam distribution and elimination half-lifes were unaltered (x t½α 1.3 hr, t½β 13.7 hr), but maximum plasma concentrations (cmax, x 2.6 ng/ml) and AUCs (x 22 hr/ng/ml) were reduced, possibly by altered plasma protein binding. No unchanged drug was detected in the urine or dialysate. In healthy subjects lormetazepam glucuronide is eliminated almost exclusively by the kidneys. In uremia, irrespective of the very low renal glucuronide clearance (x = 0.5 ml/min/1.73 m2) elimination t½ of the metabolite was only slightly prolonged (x = 80 hr). Hemodialysis had no effect on the lormetazepam kinetics. Its glucuronide was substantially removed by hemodialysis, and a dialyzer clearance of 20 ml/min could be calculated. The results indicate that in uremia lormetazepam biotransformation is not altered, but its glucuronide cumulates by a factor of 5 to 6. Clinical Pharmacology and Therapeutics (1981) 30, 77–85; doi:10.1038/clpt.1981.130
Databáze: OpenAIRE
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