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Pharmacokinetics of Sotalol Enantiomers in Humans
Author(s) -
Carr Robert A.,
Foster Robert T.,
Lewanczuk Richard Z.,
Hamilton Peter G.
Publication year - 1992
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/009127009203201208
Subject(s) - pharmacokinetics , enantiomer , chemistry , oral administration , pharmacology , stereoselectivity , sotalol , propranolol , urine , chromatography , medicine , anesthesia , stereochemistry , biochemistry , atrial fibrillation , catalysis
The chiral β‐blocker, Sotalol (STL), is marketed as a racemic mixture. Although both STL enantiomers have equal Class III antiarrythmic activity, β‐blocking activity has been ascribed mainly to the R‐enantiomer. The pharmacokinetics of STL enantiomers were studied in young (mean age 32 ± 3 years), healthy male volunteers after oral administration of 160 mg. Subsequent plasma and urine samples were collected over 24 hours, and STL enantiomer concentrations were determined using a stereospecific high‐performance liquid chromatography assay. There were no significant differences between pharmacokinetic parameters of enantiomers. The area under the time‐concentration curves (mean ± standard deviation [SD]) were 6.95 ± 0.85 and 6.76 ± 1.2 (mg/L)hour for S‐ and R‐STL, respectively. Maximal plasma concentrations of S‐ and R‐STL were 615 ± 167 and 619 ± 164 ng/mL, respectively, which were obtained on average, 3.13 ± 0.60 hours after dosing. The mean residence time (mean ± SD) was 13.2 ± 1.2 and 12.9 ± 1.8 hours for S‐and R‐STL, respectively. Respective renal clearance values for S‐ and R‐STL were 8.98 ± 1.5 and 9.46 ± 2.3 L/hour, and were approximately 1.5 times greater than creatinine clearance. Renal clearance constituted approximately 76% of the oral clearance. Although stereoselective disposition of STL was absent after racemate administration, these results should not be extrapolated to patients with significantly altered physiology, or to the pharmacokinetics of S‐STL after administration of pure‐S‐STL.