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 enantiomer with little or no activity attributed to the (+)S enantiomer. Salbutamol undergoes extensive pre-systemic metabolism and active renal excretion. 2 The pharmacokinetics of the enantiomers of salbutamol have been investigated after intravenous (1.6 mg) and oral (4 mg) dosing with racemic drug to seven normal male volunteers. Plasma and urine samples were analysed by chiral h.p.l.c. after solid phase extraction. 3 The ratio of (-)R/(+)S salbutamol in plasma and urine following intravenous 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 urine over the 8 h following an oral dose. 4 The following pharmacokinetic parameters for (+)S and (-)R salbutamol were found to be significantly 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 2.85 +/- 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 undergoes significantly faster metabolism in man than the inactive (+)S enantiomer resulting in considerably lower bioavailability of the active enantiomer following oral administration.