Interaction of citrus juices with pranidipine, a new 1,4-dihydropyridine calcium antagonist, in healthy subjects

Hashimoto, Kayoko; Shirafuji, T.; Sekino, Hisakuni; Matsuoka, Osamu; Onnagawa, O.; Okamoto, Takashi; Kudoh, Shoji; Azuma, Junichi

doi:10.1007/s002280050547

Cited by 24 publications

(10 citation statements)

References 28 publications

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“…With respect to nifedipine metabolism, nifedipine disposition is slightly affected by the expression of intestinal CYP3As because grapefruit juice influences nifedipine disposition significantly but to a lesser extent than felodipine or nisoldipine, 10,13,14 suggesting that nifedipine is mainly metabolized not in the intestine but in the liver. In addition, it is hypothesized that P-glycoprotein (P-gp) is responsible for the large interindividual difference in Table 1 Enzyme kinetic analyses of the conversion of M-I using baculovirus-expressed human ¼ P450s CYP3A5 polymorphism and nifedipne pharmacokinetics T Fukuda et al CYP3A-mediated drug disposition, since P-gp exists in the similar tissue to CYP3A4.…”

Section: Discussionmentioning

confidence: 99%

CYP3A5 genotype did not impact on nifedipine disposition in healthy volunteers

et al. 2003

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CYP3A5 expression is regulated by single-nucleotide polymorphisms (SNPs). The CYP3A5 genotype might contribute to a marked interindividual variation in CYP3A-mediated metabolism of drugs. Nifedipine is a typical substrate of CYP3A4 and CYP3A5 in vitro. The aim of this study was to elucidate the influence of the CYP3A5 genotype on nifedipine disposition in healthy subjects. A single capsule containing 10 mg of nifedipine was administered to 16 healthy male Japanese subjects (eight subjects: CYP3A5*1/*3; eight subjects: CYP3A5*3/*3). Blood samples were collected to analyze the pharmacokinetics of serum nifedipine and nitropyridine metabolite (M-I). The area under the plasma concentration-time curve (AUC), the peak plasma concentration (C max ) and the terminal half-life (t 1/2 ) of nifedipine, and the ratio of the nifedipine AUC to M-I AUC showed large intragroup variations, but no significant differences between the two genotypes. Based on the present findings, the functional relevance of CYP3A5 polymorphism should be re-evaluated in clinical trials. 2 Recently, single-nucleotide polymorphisms (SNPs) were identified in intron 3 (A-G: CYP3A5*3) and exon 7 (G-A: CYP3A5*6) of the CYP3A5 gene.3 In addition, CYP3A5*5 and CYP3A5*7 were reported as a defective allele of CYP3A5, which gave a substantial impact on CYP3A5 expression. 4,5 These SNPs cause a frame-shift mutation or alternative splicing and protein truncation, and result in the absence of CYP3A5, suggesting that only people with at least one CYP3A5*1 allele express large amounts of CYP3A5 protein. Therefore, these findings suggest that polymorphic CYP3A5 expression might be one factor contributing to the marked interindividual variation observed in CYP3A-mediated metabolism of drugs.We previously reported the frequencies of CYP3A5-related SNPs in 200 healthy Japanese subjects. 6 As a result, the allele frequency of CYP3A5*3 was approximately 70%, but CYP3A5*6 was not detected in the Japanese population. Accordingly, these findings suggested that about 40% of Japanese express relatively high levels of metabolically active CYP3A5 protein.

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Section: Discussionmentioning

confidence: 99%

CYP3A5 genotype did not impact on nifedipine disposition in healthy volunteers

et al. 2003

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“…Other dihydropyridines exhibiting the interaction to a similar extent are nisoldipine (Bailey et al, 1993b;Takanaga et al, 2000) and nicardipine . A milder but significant interaction has been detected with nitrendipine, pranidipine and nimodipine that exhibited bioavailability increments of 100, 73 and 50%, respectively (Soons et al, 1991;Fuhr et al, 1998;Hashimoto et al, 1998). However, little or no effect has been detected for nifedipine and amlodipine (Rashid et al, 1993;Josefsson et al, 1996;Vincent et al, 2000).…”

Section: Amounts and Timingmentioning

confidence: 98%

Food–drug interaction: grapefruit juice augments drug bioavailability—mechanism, extent and relevance

2003

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More than a decade has passed since it was unintentionally discovered that grapefruit juice interacts with certain drugs. The coadministration of these drugs with grapefruit juice can markedly elevate drug bioavailability, and can alter pharmacokinetic and pharmacodynamic parameters of the drug. The predominant mechanism for this interaction is the inhibition of cytochrome P-450 3A4 in the small intestine, resulting in a significant reduction of drug presystemic metabolism. An additional mechanism is, presumably, the inhibition of P-glycoprotein, a transporter that carries drug from the enterocyte back to the gut lumen, resulting in a further increase in the fraction of drug absorbed. Some calcium channel antagonists, benzodiazepines, HMG-CoA reductase inhibitors and cyclosporine are the most affected drugs. A single exposure to one glass of the juice can usually produce the maximal magnitude of the interaction. The data available so far, concerning this interaction and its clinical implications, are reviewed in this article. It is likely that more information regarding this interaction will accumulate in the future, and awareness of such is necessary for achieving optimal drug therapy.

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“…The difference in potency may be accountable in part to lack of detectable naringin 205 and 6 ′ ,7 ′ -dihydroxybergamottin 197 in orange juice. Perhaps this may partly explain why orange juice did not affect the bioavailability of orally administered nifedipine 205 or pranidipine, 206 whereas grapefruit juice signifi cantly increased their bioavailability. Nevertheless, red wine, which also contains a complex mixture of fl avonoids and other polyphenolic compounds, inhibits CYP3A4 activity in vitro .…”

Section: Effect On Cytochrome P450mentioning

confidence: 99%