ENANTIOSELECTIVE DISPOSITION OF SALBUTAMOL IN MAN FOLLOWING ORAL AND INTRAVENOUS ADMINISTRATION

1 Salbutamol is a beta(2)-adrenoceptor stimulant used clinically as a racemate where the activity resides predominantly in the (-)R enantiom er with little or no activity attributed to the (+)S enantiomer. Salbu tamol undergoes extensive pre-systemic metabolism and active renal exc retion. 2 The pharmacokinetics of the enantiomers of salbutamol have b een investigated after intravenous (1.6 mg) and oral (4 mg) dosing wit h racemic drug to seven normal male volunteers. Plasma and urine sampl es were analysed by chiral h.p.l.c. after solid phase extraction. 3 Th e ratio of (-)R/(+)S salbutamol in plasma and urine following intraven ous administration ranged from near unity soon after dosing to about 0 .66 after 8 h. The ratio remained at about 0.3 in both plasma and urin e over the 8 h following an oral dose. 4 The following pharmacokinetic parameters for (+)S and (-)R salbutamol were found to be significantl y different (P<0.05) after intravenous administration (clearance 0.39 +/- 0.12 vs 0.62 +/- 0.18 1 h(-1) kg(-1), terminal phase half-life 2.8 5 +/- 0.83 vs 2.00 +/- 0.49 h, amount excreted unchanged in urine 55 /- 11 vs 46 +/- 8%) and following oral administration (amount excreted unchanged in urine 32 +/- 11 vs 8 +/- 4% and bioavailability 0.71 +/- 0.09 vs 0.30 +/- 0.07). 5 The active (-)R enantiomer of salbutamol un dergoes significantly faster metabolism in man than the inactive (+)S enantiomer resulting in considerably lower bioavailability of the acti ve enantiomer following oral administration.