(-)-salbutamol sulphation in the human liver and duodenal mucosa: interindividual variability.
1. Salbutamol as a beta 2-adrenergic agonist used in the treatment of lung obstructive disease and premature labour. It has a bioavailability of 50% and sulphation is the main route of its metabolism. (-)-Salbutamol retains most of the beta 2-adrenergic activity and, thereby, we describe the interindividual variability in the sulphation rate of (-)-salbutamol in 100 specimens of human liver and duodenal mucosa. 2. The mean rate (pmol/min/mg of salbutamol sulphation was 498 in the duodenum and 141 in the liver with 4-fold variation within +/-2 SD units in both tissues. 3. A modelling approach based on the comparison of the best fittings obtained using a gaussian and the sum of two gaussian curves revealed the presence of two subgroups in the hepatic rate of salbutamol sulphation and their means were 69.5 and 105 pmol/min/mg (p < 0.05). In the duodenum, the rate of salbutamol sulphation approached normality. 4. The rates of salbutamol and 4-nitrophenol sulphation correlated highly (r = 0.853; p < 0.001) in the liver whereas in duodenum the rates of salbutamol and dopamine correlated highly (r = 0.914; p < 0.001), 4-Nitrophenol and dopamine are the diagnostic substrates of phenol- and catechol-sulphotransferases respectively. These findings are consistent with the view that the rate of salbutamol sulphation is higher in the gut than in liver and it varies considerably in both tissues.
Pacifici
G M
GM
Department of Biomedecine, Medical School, Pisa, Italy.
Giulianetti
B
B
Quilici
M C
MC
Spisni
R
R
Nervi
M
M
Giuliani
L
L
Gomeni
R
R
D000318:Adrenergic beta-Agonists / Q000493:pharmacokinetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000420:Albuterol / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001711:Biotransformation; D003600:Cytosol / Q000201:enzymology; D004386:Duodenum / Q000201:enzymology / Q000378:metabolism*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000201:enzymology / Q000378:metabolism*; D008099:Liver / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D013431:Sulfates / Q000378:metabolism; D015238:Sulfotransferases / Q000378:metabolism
D000318:Adrenergic beta-Agonists; D013431:Sulfates; D015238:Sulfotransferases; D000420:Albuterol