Premium
Alprazolam in end‐stage renal disease. II. Pharmacodynamics
Author(s) -
Schmith Virginia D,
Piraino Beth,
Smith Randall B,
Kroboth Patricia D
Publication year - 1992
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.1992.59
Subject(s) - alprazolam , pharmacodynamics , end stage renal disease , medicine , stage (stratigraphy) , pharmacology , intensive care medicine , pharmacokinetics , disease , biology , psychiatry , anxiety , paleontology
The sensitivity to the psychomotor and memory effects of alprazolam was evaluated in 12 normal subjects and 12 dialysis patients (seven patients receiving hemodialysis and five patients receiving continuous ambulatory peritoneal dialysis). Subjects received a single oral dose of 0.5 mg alprazolam, 2 mg alprazolam, and placebo in a double‐blind, placebo‐controlled, balanced, three‐way crossover study with a Latin square design. After administration of the test drug, blood was obtained for alprazolam concentration and protein‐binding determinations, and psychomotor performance, memory, and sedation were assessed. The maximum psychomotor impairment corrected for free alprazolam concentration was 5.0%, 8.2%, and 10.1% per nanogram per milliliter in normal subjects, patients receiving hemodialysis, and patients receiving continuous ambulatory peritoneal dialysis, respectively ( p < 0.01), after administration of 2 mg alprazolam. Free alprazolam concentrations at which 50% of maximum effect is elicited for psychomotor impairment were 10, 7.40, and 5.31 ng/ml in normal subjects, patients receiving hemodialysis, and patients receiving continuous ambulatory peritoneal dialysis, respectively. The maximum memory impairment corrected for the maximum free alprazolam concentration was 4.4%, 7.2%, and 8.9% per nanogram per milliliter, respectively ( p < 0.09), after administration of 2 mg alprazolam. Thus our group of patients receiving dialysis showed enhanced sensitivity to some psychomotor and memory effects of alprazolam. Clinical Pharmacology and Therapeutics (1992) 51 , 533–540; doi: 10.1038/clpt.1992.59