Differential inhibition of hepatic and duodenal sulfation of (-)-salbutamol and minoxidil by mefenamic acid

M. Vietri, A. Pietrabissa, R. Spisni, F. Mosca, G. M. Pacifici

Research output: Contribution to journalArticle

Abstract

Objective: The aim of this investigation was to determine whether mefenamic acid and salicylic acid inhibit the sulfation of (-)-salbutamol and minoxidil in the human liver and duodenum, and if so, to ascertain whether the 50% inhibitory concentration (IC50) estimates are different in the two tissues. Methods: Sulfotransferase activities were measured for 10 mM (-)-salbutamol and 5 mM minoxidil, and the concentration of 3'-phosphoadenosine-5'-phosphosulphate-[35S] was 0.4 μM. Results: The IC50 estimates for (-)-salbutamol and minoxidil sulfation of mefenamic acid were 72 ± 5.4 nM and 1.5 ± 0.6 μM (liver), respectively, and 161 ± 23 μM and 420 ± 18 μM (duodenum), respectively. The figures for the liver were significantly lower (P <0.0001) than those for the duodenum. The IC50 estimates for (-)-salbutamol sulfation of salicylic acid were 93 ± 11 μM (liver) and 705 ± 19 μM (duodenum, P <0.0001). Salicylic acid was a poor inhibitor of minoxidil sulfation. Conclusion: The IC50 estimates for (-)-salbutamol sulfation of mefenamic acid and salicylic acid are lower than their unbound plasma concentrations after standard dosing, suggesting that mefenamic acid and salicylic acid should inhibit the hepatic sulfation of (-)-salbutamol in vivo.

Original languageEnglish
Pages (from-to)477-479
Number of pages3
JournalEuropean Journal of Clinical Pharmacology
Volume56
Issue number6-7
Publication statusPublished - 2000

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Mefenamic Acid
Minoxidil
Albuterol
Salicylic Acid
Inhibitory Concentration 50
Duodenum
Liver
Phosphoadenosine Phosphosulfate
Sulfotransferases

Keywords

  • Intestine
  • Liver
  • Minoxidil
  • Salbutamol
  • Sulfotransferase

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

Differential inhibition of hepatic and duodenal sulfation of (-)-salbutamol and minoxidil by mefenamic acid. / Vietri, M.; Pietrabissa, A.; Spisni, R.; Mosca, F.; Pacifici, G. M.

In: European Journal of Clinical Pharmacology, Vol. 56, No. 6-7, 2000, p. 477-479.

Research output: Contribution to journalArticle

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T1 - Differential inhibition of hepatic and duodenal sulfation of (-)-salbutamol and minoxidil by mefenamic acid

AU - Vietri, M.

AU - Pietrabissa, A.

AU - Spisni, R.

AU - Mosca, F.

AU - Pacifici, G. M.

PY - 2000

Y1 - 2000

N2 - Objective: The aim of this investigation was to determine whether mefenamic acid and salicylic acid inhibit the sulfation of (-)-salbutamol and minoxidil in the human liver and duodenum, and if so, to ascertain whether the 50% inhibitory concentration (IC50) estimates are different in the two tissues. Methods: Sulfotransferase activities were measured for 10 mM (-)-salbutamol and 5 mM minoxidil, and the concentration of 3'-phosphoadenosine-5'-phosphosulphate-[35S] was 0.4 μM. Results: The IC50 estimates for (-)-salbutamol and minoxidil sulfation of mefenamic acid were 72 ± 5.4 nM and 1.5 ± 0.6 μM (liver), respectively, and 161 ± 23 μM and 420 ± 18 μM (duodenum), respectively. The figures for the liver were significantly lower (P <0.0001) than those for the duodenum. The IC50 estimates for (-)-salbutamol sulfation of salicylic acid were 93 ± 11 μM (liver) and 705 ± 19 μM (duodenum, P <0.0001). Salicylic acid was a poor inhibitor of minoxidil sulfation. Conclusion: The IC50 estimates for (-)-salbutamol sulfation of mefenamic acid and salicylic acid are lower than their unbound plasma concentrations after standard dosing, suggesting that mefenamic acid and salicylic acid should inhibit the hepatic sulfation of (-)-salbutamol in vivo.

AB - Objective: The aim of this investigation was to determine whether mefenamic acid and salicylic acid inhibit the sulfation of (-)-salbutamol and minoxidil in the human liver and duodenum, and if so, to ascertain whether the 50% inhibitory concentration (IC50) estimates are different in the two tissues. Methods: Sulfotransferase activities were measured for 10 mM (-)-salbutamol and 5 mM minoxidil, and the concentration of 3'-phosphoadenosine-5'-phosphosulphate-[35S] was 0.4 μM. Results: The IC50 estimates for (-)-salbutamol and minoxidil sulfation of mefenamic acid were 72 ± 5.4 nM and 1.5 ± 0.6 μM (liver), respectively, and 161 ± 23 μM and 420 ± 18 μM (duodenum), respectively. The figures for the liver were significantly lower (P <0.0001) than those for the duodenum. The IC50 estimates for (-)-salbutamol sulfation of salicylic acid were 93 ± 11 μM (liver) and 705 ± 19 μM (duodenum, P <0.0001). Salicylic acid was a poor inhibitor of minoxidil sulfation. Conclusion: The IC50 estimates for (-)-salbutamol sulfation of mefenamic acid and salicylic acid are lower than their unbound plasma concentrations after standard dosing, suggesting that mefenamic acid and salicylic acid should inhibit the hepatic sulfation of (-)-salbutamol in vivo.

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