Determination of nifedipine as a probe substrate of cytochrome P450 3A1/2 activity in rats

• Authors: JUŘICA Jan; TOMANDL Josef; ZAHRADNÍKOVÁ Lucia; ZENDULKA Ondřej; HADAŠOVÁ Eva
• Year of publication: 2006
• Type: Article in Proceedings
• Conference: Proceedings from XX. Biochemický zjazd
• MU Faculty or unit: Faculty of Medicine
• Field: Biochemistry
• Keywords: cytochrome P450 - nifedipine - rat
• Description: Nifedipine is a dihydropyridine calcium channel blocker used in the treatment of hypertension, acute coronary syndrom, stable angina pectoris and congestive heart failure. Oxidation of nifedipine to its pyridine metabolite is used as a valuable tool for the measurement of metabolic activity of the rat 3A1/2 or human 3A4/5 isoform of cytochrome P450. Due to high similarity in amino acid sequence between rat CYP3A1/2 and human CYP3A4/5 it is possible to predict the metabolic activity of human CYP3A4/5 by the measurement of rat CYP3A1/2 activity. Here we describe a new, very simple, rapid, sensitive and reproducible HPLC method for the determination of nifedipine and its pyridine metabolite in perfuse medium after rat liver perfusion. This method is applicable for modeling and description of possible pharmacological interactions on rat CYP3A1/2 or human CYP3A4/5, respectively.

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