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In vivo effect of diallyl sulfide and cimetidine on phenacetin metabolism and bioavailability in rat

100%

Szutowski M. M., Zalewska K., Jadczak M., Marek M.

Acta Biochimica Polonica

2002

tom 49

nr 1

Numerous cytochrome P450 inhibitors have been described as effective modulators of cytochrome P450 isoforms activity in vitro. Their inhibitory efficiency may be considerably modified after in vivo application. The aim of this study was to examine the effect of oral administration of diallyl sulfide — a cytochrome P450 2E1 inhibitor and cimetidine — a cytochrome P450 2C6 and 2C11 inhibitor on rat serum concentration of phenacetin and its metabolite acetaminophen. Both inhibitors increased area under the curve (AUC0-4h) for phenacetin by 50%. Only cimetidine reduced AUC0-4 h for acetaminophen indicating inhibition of O-deethylation activity. Quinidine — a cytochrome P450 2D subfamily and P-glycoprotein inhibitor did not change significantly phenacetin bioavailability. These results suggest that diallyl sulfide inhibits the deacetylation pathway catalysed by arylamine N-acetyl transferase. Beside cytochrome P450 1A2 other cytochrome P450 isoforms (2A6 and/or 2C11) are involved in phenacetin O-deethylation in rat.

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Paracetamol-inhibitable COX-2

67%

Botting R.

Journal of Physiology and Pharmacology

2000

tom 51

nr 4,1

Ograniczanie wyników

1 Acta Biochimica Polonica

1 Journal of Physiology and Pharmacology

1 Botting R.

1 Jadczak M.

1 Marek M.

1 Szutowski M. M.

1 Zalewska K.

1 2002

1 2000

Wyniki wyszukiwania

In vivo effect of diallyl sulfide and cimetidine on phenacetin metabolism and bioavailability in rat

Paracetamol-inhibitable COX-2