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  • High-dose short-term administration of naringin did not alter talinolol pharmacokinetics in humans.

High-dose short-term administration of naringin did not alter talinolol pharmacokinetics in humans.

European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences (2014-12-09)
M A Nguyen, P Staubach, I Tamai, P Langguth
ABSTRACT

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.

MATERIALS
Product Number
Brand
Product Description

Supelco
Naringin, analytical standard
Sigma-Aldrich
Naringin, ≥95% (HPLC)
Sigma-Aldrich
β-D-Allose, rare aldohexose sugar
Sigma-Aldrich
Naringin, ≥90% (HPLC), from citrus fruit
Naringin, European Pharmacopoeia (EP) Reference Standard
Sigma-Aldrich
Carvedilol, ≥98% (HPLC), solid
Supelco
Carvedilol, Pharmaceutical Secondary Standard; Certified Reference Material
USP
Carvedilol, United States Pharmacopeia (USP) Reference Standard
Carvedilol for system suitability, European Pharmacopoeia (EP) Reference Standard
Carvedilol, European Pharmacopoeia (EP) Reference Standard