Stereoselective sulphate conjugation of salbutamol in humans: comparison of hepatic, intestinal and platelet activity.

1. The oral bioavailability of the beta 2-adrenoceptor agonist salbutamol has been proposed to be stereoselective, presumably due to presystemic sulphate conjugation. In the present study we examined the stereochemistry of the sulphation reaction in vitro using human tissue preparations. 2. Sulphation of salbutamol was studied with partially purified hepatic M and P form phenol sulphotransferases (PSTs), 100,000 g cytosol of jejunal mucosa and platelet homogenate. The cosubstrate PAP35S was used as the sulphate donor. The acceptor substrate was either (+)-, (-)-or (+/)-salbutamol. 3. Sulphation was catalyzed by the M form PST of the liver but not the P form. The sulphation efficiency (Vmax/Km) was 11.9-fold greater for the (-)- than for the (+)- enantiomer, due entirely to a lower apparent Km for (-)-salbutamol, 103 microM, than for (+)-salbutamol, 1394 microM. 4. Sulphation by the jejunal mucosa (n = 3) was very similar to that of the M form PST with the efficiency being 9.8-fold greater for the (-)-enantiomer and apparent Km values 95 microM and 889 microM for (-)- and (+)-salbutamol, respectively. 5. Sulphation by the platelet (n = 3) was also very similar to that of the M form PST with the efficiency being 9.9-fold greater for the (-)-enantiomer and apparent Km values 141 microM and 1190 microM for (-)- and (+)-salbutamol, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)