The β2-adrenergic agonist salbutamol is administered by inhalation to treat lung-obstructive disease. Salbutamol is metabolized by conjugation with sulphate, and the sulphation of salbutamol was investigated in human lung. Specimens of lung were obtained at lobectomy from 11 non-smokers, 39 smokers and 46 ex-smokers, the latter refraining from smoking at least 6 months before surgery. Neither sex nor ageing influenced the activity of sulphotransferase. The rate of salbutamol sulphation (pmol·min-1·mg-1) was greater in non-smokers (27.7) than in smokers (21.3), whereas it was similar in smoker and ex-smokers (22.8). The rate of salbutamol sulphation ranged up to six fold and its distribution did not deviate from normality. As the rate of formation of the inactive salbutamol sulphate varied in the lung, the availability of salbutamol and, in turn, the evoked pharmacological effect should vary in parallel. The activities of salbutamol and dopamine sulphotransferase correlated, suggesting that catechol sulphotransferase takes part in the sulphation of salbutamol. The sulphation of salbutamol is stereoselective in the human lung, the k M estimate for (+)-salbutamol (1198 μM) being greater than those for either (-)-salbutamol (190 μM) and racemic salbutamol (142 μM). These results are consistent with the view that (-)-salbutamol is a better substrate than (+)-salbutamol for sulphotransferase.
This is a preview of subscription content, log in to check access.
Buy single article
Instant access to the full article PDF.
Price includes VAT for USA
Subscribe to journal
Immediate online access to all issues from 2019. Subscription will auto renew annually.
This is the net price. Taxes to be calculated in checkout.
Anderson RL, Weinshilboum MR (1980) Phenol-sulphotransferase in human tissues: Radiochemical enzymatic assay and biochemical properties. Clin Chim Acta 103:79–90.
Baranczyk-Kuzma A (1986) Phenol sulphotransferase in human lung. Biochem Med Metab Biol 35:18–30.
Bliss CI (1967) Statistics in biology, vol 1. McGraw-Hill, New York, pp 101–110.
Brittain RT, Farmer JB, Marshall RJ (1973) Some observations on the β-adrenoceptor agonist properties of the isomers of salbutamol. Br J Pharmacol 48:144–147.
Cappiello M, Giuliani L, Pacifici GM (1990) Differential distribution of phenol- and catechol- sulphotransferases in human liver and intestinal mucosa. Pharmacology 40:69–76.
Cappiello M, Giuliani L, Rane A, Pacifici GM (1991) Dopamine sulphotransferase is better developed than p-nitrophenol sulphotransferase in the human fetus. Dev Pharmacol Toxicol 16:83–88.
Dixon WJ, Massey FJ, Jr. (1983) Introduction to statistical analysis, 4th edn. McGraw-Hill, New York, pp 64–66.
Foldes A, Meek JK (1973) Rat brain phenolsulphotransferase partial purification and some properties. Biochim Biophys Acta 327:365–374.
Hartley D, Middlemiss D (1971) Absolute configuration of the optical isomers of salbutamol. J Med Chem 14:895–896.
Hawkins CJ, Klease GT (1973) Relative potency of (-)- and (+)-salbutamol on guinea pig tracheal tissues. J Med Chem 16:856–857.
Lowry OH, Rosebrough NJ, Farr A, Randall RJ (1951) Protein measurement with folin phenol reagent. J Biol Chem 193:265–275.
Morgan DJ, Paull JD, Richmond BH, Wilson-Evered E, Ziccone SP (1986) Pharmacokinetics of intravenous and oral salbutamol and its sulphate conjugate. Br J Clin Pharmacol 22:587–593.
Pacifici GM, Eligi M, Giuliani L (1993) (+) and (-) Terbutaline are sulphated at a higher rate in human intestine than in liver. Eur J Clin Pharmacol 45:483–487.
Pacifici GM, Temellini A, Castiglioni M, D'Alessandro C, Ducci A, Giuliani L (1994) Interindividual variability of the human hepatic sulphotransferases. Chem-Biol Interact 92:219–231.
Pesola GR, Walle T (1992) Enantiomeric interaction in the sulphate conjugation of the β2-agonist drug albuterol by the human liver. Res Comm Chem Pathol Pharmacol 75:125–128.
Shapiro SS, Wilk MD (1965) An analysis test for normality (complete samples). Biometrika 52:591–611.
Tan YK, Soldin SJ (1987) Analysis of salbutamol enantiomers in human urine by chiral high-performance liquid chromatography and preliminary studies related to the stereoselective disposition kinetics in man. J Chromatogr 422:187–195.
Walle UK, Pesola GR, Walle T (1993) Stereoselective sulphate conjugation of salbutamol in humans: comparison of hepatic, intestinal and platelet activity. Br J Clin Pharmacol 35:413–418.
About this article
Cite this article
Pacifici, G.M., De Santi, C., Mussi, A. et al. Interindividual variability in the rate of salbutamol sulphation in the human lung. Eur J Clin Pharmacol 49, 299–303 (1996). https://doi.org/10.1007/BF00226331