(-)-Salbutamol sulphation in the human liver and duodenal mucosa : interindividual variability

• Published in: Xenobiotica Vol. 27; no. 3; pp. 279 - 286
• Main Authors: PACIFICI, G. M., GIULIANETTI, B., QUILICI, M. C., SPISNI, R., NERVI, M., GIULIANI, L., GOMENI, R.
• Format: Journal Article
• Language: English
• Published: London Informa UK Ltd 1997; Taylor & Francis
• Subjects: Adrenergic beta-Agonists - pharmacokinetics; Adult; Aged; Aged, 80 and over; Albuterol - pharmacokinetics; Area Under Curve; Biological and medical sciences; Biotransformation; Cytosol - enzymology; Duodenum - enzymology; Duodenum - metabolism; Female; Humans; In Vitro Techniques; Intestinal Mucosa - enzymology; Intestinal Mucosa - metabolism; Liver - enzymology; Liver - metabolism; Male; Medical sciences; Middle Aged; Pharmacology. Drug treatments; Respiratory system; Sulfates - metabolism; Sulfotransferases - metabolism; Human; Duodenum; Liver; Tissue specificity; β-Adrenergic receptor agonist; Bioavailability; Antiasthma agent; Metabolism; In vitro; Sulfatation; Interindividual comparison; Salbutamol; Pharmacokinetics
• ISSN: 0049-8254; 1366-5928
• DOI: 10.1080/004982597240604

1. Salbutamol is a β2-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 β2-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.