STEREOSELECTIVE DISPOSITION OF (+ -)-SOTALOL AT STEADY-STATE CONDITIONS/

The objective of this study was to assess, under steady-state conditio ns, the stereoselective disposition of (+/-)-sotalol in man. In all pa tients studied (n = 7) values of oral clearance (137 +/- 51 ml min-1), renal clearance (96 +/- 42 ml min-1) and nonrenal clearance (41 +/- 2 5 ml min-1) of (-)-sotalol were greater than those for (+)-sotalol (12 3 +/- 45 ml min-1, 89 +/- 39 ml min-1 and 34 +/- 23 ml min-1, respecti vely; P < 0.05, Student's paired t-test). Binding to plasma proteins w as greater for (+)-sotalol (38 +/- 9% vs 35 +/- 9% for the (-)-enantio mer; 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 clearanc e, which represents almost-equal-to 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 differen ce in the pharmacokinetics of sotalol enantiomers is mainly related to stereoselectivity in plasma protein binding.