Relationship between Lipophilicities of 1, 4-Dihydropyridine Derivatives and Pharmacokinetic Interaction Strengths with Grapefruit Juice

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概要

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• It is well known fact that the strengths of drug interactions with grapefruit juice (GFJ) differ greatly depending on the 1, 4-dihydropyridine calcium channel antagonist (DHP) used. However, there are no available data on the relationship between interactions with GFJ and its physicochemical attributes. Therefore we endeavored to study the correlation between calculated logP values, indicating lipophilicity, from chemical structures of DHPs as well as water diffusion, molecular volume, molecular polarization, molecular density, refractive index, topologic polar surface area, and calculated molar refractivity. Thirteen forms of DHP, amlodipine, azelnidipine, benidipine, cilnidipine, efonidipine, felodipine, manidipine, nicardipine, nifedipine, nimodipine, nisoldipine, nitrendipine, and pranidipine were analyzed due to clinical trials performed with GFJ and these agents. The pharmacokinetic interaction strengths were defined in common logarithmic values of increasing ratios of area under the plasma concentration-time curve (AUC) with GFJ intake compared with controls. Physicochemical properties including three categories of predicted logP values were calculated from the structures of DHPs and their estimated relationship with the interactions. As a result, the logP values indicated significant positive correlations with the interaction strengths. This finding suggests that lipophilicity is an important factor in the strengths of pharmacokinetic interactions of DHPs with GFJ intake.

• 公益社団法人日本薬学会の論文
• 2008-01-01

著者

• Uesawa Yoshihiro

  Clinical Pharmaceutics Laboratory Department Of Pharmaceutics Meiji Pharmaceutical University

• Mohri Kiminori

  Clinical Pharmaceutics Laboratory Department Of Pharmaceutics Meiji Pharmaceutical University

• 植沢 芳広

  Clinical Pharmaceutics Laboratory, Department of Pharmaceutics, Meiji Pharmaceutical University

• 毛利 公則

  Clinical Pharmaceutics Laboratory, Department of Pharmaceutics, Meiji Pharmaceutical University

関連論文

• Metabolism of bucolome in rats Stability and biliary excretion of bucolome N-glucuronide
• The Use of Heat Treatment to Eliminate Drug Interactions Due to Grapefruit Juice(Biopharmacy)
• Relationship between Lipophilicities of 1, 4-Dihydropyridine Derivatives and Pharmacokinetic Interaction Strengths with Grapefruit Juice
• UV-Irradiated Grapefruit Juice Loses Pharmacokinetic Interaction with Nifedipine in Rats(Biopharmacy)

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