Nguyen M A, Staubach P, Tamai I, Langguth P
Institute of Pharmacy, Johannes Gutenberg University, Staudingerweg 5, 55099 Mainz, Germany.
Department of Dermatology, Clinical Research Center, University Medical Center, Langenbeckstraße 1, 55101 Mainz, Germany.
Eur J Pharm Sci. 2015 Feb 20;68:36-42. doi: 10.1016/j.ejps.2014.12.001. Epub 2014 Dec 5.
Naringin is considered the major causative ingredient of the inhibition of intestinal drug uptake by grapefruit juice. Moreover, it is contained in highly dosed nutraceuticals available on the market. A controlled, open, randomized, crossover study was performed in 10 healthy volunteers to investigate the effect of high-dose naringin on the bioavailability of talinolol, a substrate of intestinal organic anion-transporting polypeptide (OATP)-mediated uptake. Following 6-day supplementation with 3 capsules of 350 mg naringin daily, 100mg talinolol were administered orally with 3 capsules of the same dietary supplement (1050 mg naringin) on the seventh day. This test treatment was compared to 100mg talinolol only (control). The results showed that short-term high-dose naringin supplementation did not significantly affect talinolol pharmacokinetics. Geometric mean ratios of test versus control ranged between 0.90 and 0.98 for talinolol c(max), AUC(0-48 h), AUC(0-∞), t(1/2) and A(e(0-48 h)). The high dose may provoke inhibition of the efflux transporter P-glycoprotein (P-gp) which counteracts the uptake inhibition. As disintegration and dissolution processes are required for the solid dosage form, dissolved naringin may arrive at the site of interaction after talinolol is already absorbed. In conclusion, the effect of nutraceuticals on drug pharmacokinetics can deviate from that observed when administered as food component due to the different dose and dosage form.
柚皮苷被认为是葡萄柚汁抑制肠道药物吸收的主要致病成分。此外，市场上高剂量的营养保健品中也含有柚皮苷。对10名健康志愿者进行了一项对照、开放、随机、交叉研究，以调查高剂量柚皮苷对他林洛尔生物利用度的影响，他林洛尔是肠道有机阴离子转运多肽（OATP）介导的摄取的底物。在每天补充3粒350毫克柚皮苷胶囊6天后，第7天口服100毫克他林洛尔并同时服用3粒相同的膳食补充剂（1050毫克柚皮苷）。将这种试验性治疗与仅服用100毫克他林洛尔（对照）进行比较。结果表明，短期高剂量补充柚皮苷对他林洛尔的药代动力学没有显著影响。他林洛尔的C(max)、AUC(0 - 48 h)、AUC(0 - ∞)、t(1/2)和A(e(0 - 48 h))的试验组与对照组的几何平均比值在0.90至0.98之间。高剂量可能会引发外排转运体P-糖蛋白（P-gp）的抑制，这抵消了摄取抑制作用。由于固体剂型需要崩解和溶解过程，溶解的柚皮苷可能在他林洛尔已经吸收后才到达相互作用部位。总之，由于剂量和剂型不同，营养保健品对药物药代动力学的影响可能与作为食物成分给药时观察到的情况不同。
