Pharmacokinetic interaction of calcitriol with 20(S)-protopanaxadiol in mice: Determined by LC/MS analysis.

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ID: 32172
2019
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Ranked #35 of 60 articles by views in European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences

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Abstract
The physiological and anti-cancer functions of vitamin D are accomplished primarily via 1α,25-dihydroxyvitamin D (calcitriol), whereas 20(S)-protopanaxadiol (aPPD) is a ginsenoside, which is isolated from Panax ginseng, with potential anti-cancer benefits. In the present study, we report a pharmacokinetic (PK) herb-nutrient interaction between calcitriol and aPPD in mice. A liquid chromatography mass spectrometry (LC/MS) method was developed using 4-phenyl-1,2,4-triazoline-3,5-dione derivatizing agent and we subsequently used the method to quantitate calcitriol in mouse serum. The limit of quantitation was 0.01 ng/ml which is approximately 100 fold lower than the previously reported assay from our laboratory. Calcitriol PK parameters were determined in non-tumor-bearing or C4-2 human prostate tumor-bearing nude mice following oral co-administration of calcitriol either alone or in combination with aPPD. Mice were pretreated with oral aPPD (70 mg/kg) or vehicle control twice daily for seven consecutive days, followed by a single oral dose of 4 μg/kg calcitriol alone or in combination with aPPD. Our PK results demonstrated that co-administration of calcitriol with aPPD (following pre-treatment with vehicle for seven days) resulted in a 35% increase in the area under the curve (AUC) and a 41% increase in the maximum serum concentration (Cmax) compared to the calcitriol only group. aPPD therefore significantly increased calcitriol serum exposure. We also saw a reduction in the time required to reach Cmax. In contrast, calcitriol PK in mice co-administered with calcitriol and aPPD as well as those pretreated seven consecutive days with aPPD was no different than that determined for the mice that received vehicle for seven days as pre-treatment. Co-administration of calcitriol with aPPD therefore could increase health benefits of vitamin D, however any increased risk of hypercalcemia, resulting from this combination approach, requires further investigation. Lastly, we surmise that a cytochrome P450 inhibition-based mechanism may contribute to the observed PK interaction.
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beneltriki2019pharmacokineticeuropean Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Ben-Eltriki, Mohamed;Hassona, Mohamed;Meckling, Gray;Adomat, Hans;Deb, Subrata;Tomlinson Guns, Emma S;
Journal European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences
Year 2019
DOI
S0928-0987(19)30024-7
URL
Keywords Keywords not found

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