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Stereoselective disposition of (+/‐)‐sotalol at steady‐state conditions.
Author(s) -
Fiset C.,
Philippon F.,
Gilbert M.,
Turgeon J.
Publication year - 1993
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/j.1365-2125.1993.tb05896.x
Subject(s) - sotalol , stereoselectivity , pharmacokinetics , chemistry , enantiomer , steady state (chemistry) , pharmacology , clearance , oral administration , medicine , urology , stereochemistry , biochemistry , atrial fibrillation , catalysis
The objective of this study was to assess, under steady‐state conditions, the stereoselective disposition of (+/‐)‐sotalol in man. In all patients studied (n = 7) values of oral clearance (137 +/‐ 51 ml min‐1), renal clearance (96 +/‐ 42 ml min‐1) and nonrenal clearance (41 +/‐ 25 ml min‐1) of (−)−sotalol were greater than those for (+)‐sotalol (123 +/‐ 45 ml min‐1, 89 +/‐ 39 ml min‐1 and 34 +/‐ 23 ml min‐1, respectively; P < 0.05, Student's paired t‐test). Binding to plasma proteins was greater for (+)‐sotalol (38 +/‐ 9% vs 35 +/‐ 9% for the (−)−enantiomer; P < 0.05) such that unbound oral clearance (+)/(‐) ratio (0.95 +/‐ 0.06) and unbound renal clearance (+)/(‐) ratio (0.97 +/‐ 0.06) were not stereoselective. In contrast, estimated unbound nonrenal clearance, which represents approximately 25% of the total unbound clearance of the drug, was greater for the (−)−enantiomer (64 +/‐ 42 ml min‐1) compared with (+)‐sotalol (57 +/‐ 42 ml min‐1; P < 0.05). The difference in the pharmacokinetics of sotalol enantiomers is mainly related to stereoselectivity in plasma protein binding.