Pharmacokinetics and pharmacodynamics of dilevalol.
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 beta-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 less than 0.05) and an 11% increase in systemic bioavailability (p less than 0.05) after oral administration. Dilevalol caused significant cardiac beta-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.
Tenero
D M
DM
Department of Clinical Pharmacy, University of Tennessee, Memphis 38163.
Bottorff
M B
MB
Given
B D
BD
Kramer
W G
WG
Affrime
M B
MB
Patrick
J E
JE
Lalonde
R L
RL
D000284:Administration, Oral; D000328:Adult; D000704:Analysis of Variance; D001682:Biological Availability; D001794:Blood Pressure / Q000187:drug effects*; D002927:Cimetidine / Q000494:pharmacology*; D004347:Drug Interactions; D004562:Electrocardiography; D006207:Half-Life; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D007275:Injections, Intravenous; D007741:Labetalol / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D016018:Least-Squares Analysis; D008297:Male; D014018:Tissue Distribution; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology
D014665:Vasodilator Agents; D002927:Cimetidine; D007741:Labetalol