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Pharmacokinetics and pharmacodynamics of dilevalol
Author(s) -
Tenero David M,
Bottorff Michael B,
Given Bruce D,
Kramer William G,
Affrime Melton B,
Patrick James E,
Lalonde Richard L
Publication year - 1989
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.1989.201
Subject(s) - pharmacokinetics , cimetidine , labetalol , pharmacology , pharmacodynamics , volume of distribution , medicine , bioavailability , oral administration , propranolol , drug interaction , clinical pharmacology , anesthesia , blood pressure
The pharmacokinetics and pharmacodynamics of dilevalol, the R,R stereoisomer of labetalol, were evaluated in nine subjects. Dilevalol was given as a single 50 mg intravenous dose and as a 400 mg daily oral dose for 7 days. To study the effects of hepatic enzyme inhibition, each subject received dilevalol in the presence of and absence of cimetidine. Cardiac β‐blockade was assessed by use of standardized treadmill tests for 48 hours after oral dilevalol. The three‐compartment model analysis showed that systemic clearance (29.8 ± 5.7 ml/min/kg), volume of distribution (16.6 ±4.1 L/kg), and terminal half‐life (11.7 ± 2.7 hours) were not altered by cimetidine. However, there was a 20% increase in the area under the curve ( p < 0.05) and an 11% increase in systemic bioavailability ( p < 0.05) after oral administration. Dilevalol caused significant cardiac β‐blockade for more than 24 hours, but these effects were not altered by cimetidine. The pharmacokinetic changes are consistent with a decrease in first‐pass extraction of a high clearance drug. Clinical Pharmacology and Therapeutics (1989) 46 , 648–656; doi: 10.1038/clpt.1989.201