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Propranolol interactions with diazepam, lorazepam, and alprazolam
Author(s) -
Ochs Hermann R,
Greenblatt David J,
VerburgOchs Birgitt
Publication year - 1984
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.1984.203
Subject(s) - diazepam , lorazepam , alprazolam , propranolol , chemistry , pharmacology , metabolite , pharmacokinetics , glucuronide , medicine , anesthesia , anxiety , psychiatry , biochemistry
Healthy subjects received single doses of diazepam (5 to 10 mg iv), lorazepam (2 mg iv), or alprazolam (1 mg orally) on two occasions, once in the control state and once with propranolol, 80 mg three times a day. Compliance with the propranolol regimen was verified by measurement of serum propranolol levels (overall X̄: 100 ng/ml) and by reduction in sensitivity to intravenous metaproterenol to one‐thirtieth that of the control value. Propranolol prolonged diazepam elimination t½ (58 and 49 hr), reduced its clearance (0.20 and 0.24 ml/min/kg), and increased the 168‐hr AUC for desmethyldiazepam, the major metabolite of diazepam (5.63 and 4.81 µg/ml · hr). Propranolol had no significant effect on lorazepam t½ (13.2 and 12.7 hr) or clearance (1.33 and 1.36 ml/min/kg), nor on alprazolam t½ (15.9 and 18.5 hr) or clearance (1.1 and 0.8 ml/min/kg). Thus propranolol induces a small but significant reduction in clearance of diazepam, biotransformed mainly by the oxidative reaction of N ‐demethylation. Propranolol does not impair lorazepam clearance by glucuronide conjugation nor that of alprazolam by aliphatic hydroxylation. Clinical Pharmacology and Therapeutics (1984) 36, 451–455; doi: 10.1038/clpt.1984.203