Food-drug interaction of tacrolimus with pomelo, ginger, and turmeric juice in rats.
ABSTRACT Tacrolimus is a well-known potent immunosuppressant agent, which has various drug-drug or food-drug interactions. Previously, we found a renal transplant recipient who increased tacrolimus blood concentrations after ingestion of pomelo as a rare case. So, we investigated the effect of pomelo after its administration for one day or 3 consecutive days on the pharmacokinetics of tacrolimus in rats. We also confirmed the effects of grapefruit, turmeric, and ginger. The tacrolimus blood concentrations of the rats pre-treated with 100% pomelo juice were significantly higher than those pre-treated with water. On the other hand, the tacrolimus blood concentrations of the rats pre-treated with 50% pomelo juice were not significantly different from those pre-treated with water. The pomelo-tacrolimus interaction showed concentration dependency. Even low concentration of pomelo juice could enhance the blood concentrations of tacrolimus by repeated administration. The inhibitory effect of 100% pomelo juice disappeared 3 days after intake. The AUC values of tacrolimus in the rats pre-treated with grapefruit juice, ginger juice, and turmeric juice were significantly larger than those pre-treated with water. We could confirm the pomelo-tacrolimus interaction, which we discovered in a case study, quantitatively. We newly found the influence of turmeric and ginger on tacrolimus pharmacokinetics, comparable to pomelo.
Alternative and Complementary Therapies 12/2013; 19(6):315-322. DOI:10.1089/act.2013.19605
[Show abstract] [Hide abstract]
ABSTRACT: Concerns about ethnicity-related differences have resulted in a significant “drug lag” in regulatory approvals. The International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) document on Ethnic Factors in the Acceptability of Foreign Clinical Data, ICH E5, provides guidelines for assessing ethnicity as a cause of differences in drug treatment and using bridging strategies to avoid unnecessary duplication of clinical trials without compromising the quality, safety, and efficacy of the drug, with the goal of expediting the drug approval process. However, these guidelines have not been fully adopted by all countries, and there are differences in the way the bridging concept is applied. An approach that may provide the resolution to this dilemma is the multi-regional parallel bridging method, or simultaneous drug development. However, the definition of ethnicity is currently too vague and imprecise for clinical trial data to be easily understood and extrapolated across borders. The integration of pharmacogenomics and biomarkers in drug development may provide greater clarity to the characterization of drug response variability between populations.Pharmacogenomics, Edited by Lam, Y.-W. F. & Cavallari, L. H., 01/2013: chapter 10- The Importance of Ethnicity Definitions and Pharmacogenomics in Ethnobridging: pages 367-404; Academic Press, San Diego., ISBN: 978-0-12-391918-2
[Show abstract] [Hide abstract]
ABSTRACT: The aim of this study was to investigate the effect of pomelo pulp on the pharmacokinetics of cyclosporine in healthy male Thai volunteers.The study design was an open-label, randomized, single dose, crossover study with a twoweek washout period. A single oral dose of 2×100 mg cyclosporine was administered with 200 ml of water. Each subject received 250 g of pomelo pulp or 250 ml of water 1 h before drug administration and once again 10 min following drug administration. Blood samples were collected over a 24 h period. The point estimates (90% confidence intervals) of the test/control ratio using logarithmic transformed data for the area under the curve (AUC) for blood concentration from time 0 to infinity (AUC0-∞) and the observed maximum concentration (Cmax) were 128.8% (120.6-137.6) and 136.1%(126.0-146.8), respectively. These 90% confidence intervals were higher than the accepted bioequivalence range defined by the European Medicines Agency guidelines for narrow therapeutic index drugs (90-111% for AUC and 80-125% for Cmax). However, the apparent terminal half-life (t1/2) was not significantly different.In conclusion, co-administration of cyclosporine and pomelo pulp increased the relative bioavailability of cyclosporine. This article is protected by copyright. All rights reservedThe Journal of Clinical Pharmacology 04/2015; 55(4). DOI:10.1002/jcph.430 · 2.47 Impact Factor