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Stereospecific evaluation of sotalol pharmacokinetics in a rat model: Evidence suggesting an enantiomeric interaction
Author(s) -
Carr R. A.,
Pasutto F. M.,
Foster R. T.
Publication year - 1994
Publication title -
biopharmaceutics and drug disposition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.419
H-Index - 58
eISSN - 1099-081X
pISSN - 0142-2782
DOI - 10.1002/bdd.2510150203
Subject(s) - enantiomer , stereospecificity , pharmacokinetics , sotalol , chemistry , pharmacology , racemic mixture , oral administration , stereochemistry , medicine , biochemistry , atrial fibrillation , catalysis
Sotalol (STL) is a chiral β‐adrenergic blocking drug, which is useful clinically as the racemate in treating hypertension, and is also useful as a class III antiarrhythmic when administered as the pure S‐enantiomer. Utilizing a stereospecific high‐performance liquid chromatographic (HPLC) assay, the enantiomeric disposition of STL is reported after administration of racemate and both pure enantiomers to a rat model. After administration of the racemate, enantiomers of STL had similar plasma concentration‐time profiles. Following administration of the pure S‐enantiomer of STL, however, systemic clearance was significantly reduced; R‐STL disposition after pure enantiomer administration was not significantly altered. Changes in systemic clearance of S‐STL after either racemate or enantiomer dosing were explained by corresponding changes in renal clearance. Renal clearance values of S‐STL were significantly reduced from 33·7 ± 6·0 to 28·9 ± 5·6 ml min −1 kg −1 for administration as racemate and pure enantiomer, respectively. As clearance of STL approximates reported values of renal blood flow, renal perfusion changes caused by the β‐blocking effects of R‐STL may explain changes in S‐STL disposition. It is suggested that dosing of STL as either racemate or pure enantiomer, depending on the clinical indication for use, may result in significantly altered enantiomer disposition.