Nifedipine Grapefruit juice

Calcium antagonists (felodipine, nifedipine, Grapefruit juice Increased bioavailability inhibition of first-pass... 

Mohri K, Uesawa Y. Effects of furanocoumarin derivatives in grapefruit juice on nifedipine pharmacokinetics in rats. Pharm Res 2001 18(2) 177-182. 

Sigusch H, Hippius M, Henschel L, Kaufmann K, Hoffmann A. Influence of grapefruit juice on the pharmacokinetics of a slow release nifedipine formulation. Pharmazie 1994 49(7) 522-524. 

Coadministration of nifedipine with grapefruit juice is to be avoided (see Clinical Pharmacology and Precautions )... 

Grapefruit juice Coadministration of nifedipine with grapefruit juice results in up to a twofold increase in AUC and Cmax) due to inhibition of CYP3A4-related first-pass metabolism. This effect of grapefruit juice may last for at least three days. Administration of nifedipine with grapefruit juice is to be avoided... 

Coadministration of nifedipine and grapefruit juice resulted in an approximately twofold increase in nifedipine area under the curve (AUC) and Cmax with no change in half-life. The increased plasma concentrations are most likely due to the inhibition of CYP3A4-related first-pass metabolism. 

Appropriate information on grapefruit juice interaction appears in product labeling estrogens, lovastatin, nifedipine, and verapamil. 

Nifedipine was one of the first CYP3A4 substrates to be identified (167,168) and has been the subject of a large number of drug-drug interaction studies both in vitro and in vivo. Pharmacokinetic studies with nifedipine clearly identify inhibitors, such as itraconazole (169) and grapefruit juice (170), and inducers, such as the barbiturates (171) and rifampin (172). 

Cytochrome P450 3A4 is highly expressed in the human small intestinal mucosa, and is responsible for the metabolism of cyclosporine, midazolam, clozapine and saquinavir during passage across the intestinal mucosa. Indeed, inhibition of presystemic metabolic processes is likely to be a factor in a 34% to 103% increase in the bioavailability of nifedipine observed in individuals consuming grapefruit juice. 

CALCIUM CHANNEL BLOCKERS GRAPEFRUIT JUICE t bioavailability of felodipine and nisoldipine (with reports of adverse effects), and t bioavailability of isradipine, lacidipine, lercanidipine, nicardipine, nifedipine, nimodipine and verapamil (without reported adverse clinical effects) Postulated that flavonoids in grapefruit juice (and possibly Seville oranges and limes) inhibit intestinal (but not hepatic) CYP3A4. They also inhibit intestinal P-gp, which may t the bioavailability of verapamil Avoid concurrent use of felodipine and nisoldipine and grapefruit juice... 

Hashimoto Y, Kuroda T, Shimizu A, Hayakava M, Fukuzaki H, Morimoto S. Influence of grapefruit juice on plasma concentration of nifedipine. Jpn J Clin Pharmacol Ther 1996 27 599-606. 

Effects of grapefruit juice on the pharmacokinetics of the calcium channel blockers nifedipine and nisoldipine. Curr Ther Res Clin Exp 1998 59 619-34. 

Azuma J, Yamamoto I, Wafase T, Orii Y, Tinigawa T, Terashima S, Yoshikawa K, Tanaka T, Kawano K. Effects of grapefruit juice on the pharmacokinetics of the calcium channel blockers nifedipine and nisoldipine. Curr Ther Res Clin Exp 1998 59 619-34. 

CYP3A, does not contribute to the interaction between nifedipine and grapefruit juice. Br. J. Clin. Pharmacol. 36 460-63... 

CYP3A3/4 Cyclosporine Verapamil Nifedipine blockers Phenytoin Rifampin Barbiturates Erythromycin Verapamil Ketoconazole Grapefruit juice (Yes)" Erythromcyin Midazolam... 

Targeted questions depending on suspected diagnosis (e.g., aspirin use in stroke patients grapefruit juice in elderly patient with hypotension and nifedipine, antipsychotic or antiemetic medication in Parkinson s disease). 

Compounds in grapefruit juice such as naringenin and 6. 7 -dihydroxybergamottin can increase the rate and extent of bioavailability of several dihydropyridine calcium channel blockers, including felodipine and nifedipine. This interaction may be due to inhibition of the metabolism of the dihydropyridines by intestinal wall CYP3A4 or inhibition of the P-glycoprotein transporter in the same location. The answer is (C). 

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