Interindividual variability in the rate of salbutamol sulphation in the human lung.
The beta2-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 center dot min-1 center dot 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 kM estimate for (+)- salbutamol (1198 mu M) being greater than those for either (-)-salbutamol (190 mu M) and racemic salbutamol (142 mu M). These results are consistent with the view that (-)-salbutamol is a better substrate than (+)-salbutamol for sulphotransferase.
Pacifici
G M
GM
Department of Biomedicine, Medical School, Pisa, Italy.
De Santi
C
C
Mussi
A
A
Ageletti
C A
CA
D000318:Adrenergic beta-Agonists / Q000737:chemistry / Q000378:metabolism*; D000368:Aged; D000420:Albuterol / Q000737:chemistry / Q000378:metabolism*; D005260:Female; D006801:Humans; D008168:Lung / Q000166:cytology / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D008968:Molecular Conformation; D015238:Sulfotransferases / Q000493:pharmacokinetics
D000318:Adrenergic beta-Agonists; D015238:Sulfotransferases; D000420:Albuterol