Stereoselective disposition of (+/-)-sotalol at steady-state conditions.
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.
Fiset
C
C
Ecole de Pharmacie, Université Laval, Ste-Foy, Québec, Canada.
Philippon
F
F
Gilbert
M
M
Turgeon
J
J
D000328:Adult; D000368:Aged; D001798:Blood Proteins / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D003404:Creatinine / Q000097:blood; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011485:Protein Binding; D013015:Sotalol / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D013237:Stereoisomerism
D001798:Blood Proteins; D013015:Sotalol; D003404:Creatinine