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Effects of uremia and hemodialysis on lormetazepam disposition
Author(s) -
Kampf Dieter,
Huempel Michael,
Lerche Ursula,
Kessel Michael
Publication year - 1981
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.1981.130
Subject(s) - uremia , hemodialysis , pharmacokinetics , chemistry , cmax , dialysis , glucuronide , metabolite , pharmacology , urine , endocrinology , medicine , urology
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 (x̄ t½α 1.3 hr, t½β 13.7 hr), but maximum plasma concentrations (c max , x̄ 2.6 ng/ml) and AUCs (x̄ 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 (x̄ = 0.5 ml/min/1.73 m 2 ) elimination t½ of the metabolite was only slightly prolonged (x̄ = 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