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Bromazepam pharmacokinetics: Influence of age, gender, oral contraceptives, cimetidine, and propranolol
Author(s) -
Ochs Hermann R,
Greenblatt David J,
Friedman H,
Burstein Ethan S,
Locniskar Ann,
Harmatz Jerold S,
Shader Richard I
Publication year - 1987
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.1987.72
Subject(s) - bromazepam , pharmacokinetics , volume of distribution , cimetidine , volunteer , propranolol , drug interaction , oral administration , medicine , chemistry , endocrinology , benzodiazepine , pharmacology , receptor , agronomy , biology
Pharmacokinetics of the benzodiazepine bromazepam were evaluated in volunteer subjects who received single 6 mg oral doses followed by blood sampling during the next 48 hours. Age and gender effects were studied in 32 subjects, divided into young (aged 21 to 29 years) and elderly (aged 60 to 81 years) groups. Compared with young subjects, the elderly had significantly higher peak serum bromazepam concentrations (132 vs. 82 ng/ml), smaller volume of distribution (0.88 vs. 1.44 L/kg), lower oral clearance (0.41 vs. 0.76 ml/min/kg), and increased serum free fraction (34.8% vs. 28.8% unbound). However, gender had no significant influence on bromazepam kinetics. In 11 young female users of oral contraceptive steroids, compared with seven age‐ and weight‐matched control women not using oral contraceptives, no differences in bromazepam kinetics were observed. Coadministration of cimetidine (1.2 gm daily) significantly reduced bromazepam clearance (0.41 vs. 0.82 ml/min/kg) and prolonged elimination half‐life (29 vs. 23 hours). Propranolol (160 mg daily) significantly prolonged bromazepam half‐life (28 vs. 23 hours), but the reduction in clearance associated with propranolol (0.65 vs. 0.82 ml/min/kg) did not reach significance. Bromazepam has the pharmacokinetic characteristics of benzodiazepines with half‐life values between 20 and 30 hours. Consistent with its biotransformation pathway by hepatic microsomal oxidation, bromazepam clearance is significantly impaired in elderly individuals, by coadministration of cimetidine and possibly propranolol. Clinical Pharmacology and Therapeutics (1987) 41, 562–570; doi: 10.1038/clpt.1987.72