title: High-dose short-term administration of naringin did not alter talinolol pharmacokinetics in humans.
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.
authors.affiliation: Institute of Pharmacy, Johannes Gutenberg University, Staudingerweg 5, 55099 Mainz, Germany.
authors.forename: M A
authors.initials: MA
authors.lastname: Nguyen
authors.affiliation: Department of Dermatology, Clinical Research Center, University Medical Center, Langenbeckstraße 1, 55101 Mainz, Germany.
authors.forename: P
authors.initials: P
authors.lastname: Staubach
authors.affiliation: Institute of Medical, Pharmaceutical and Health Sciences, Faculty of Pharmaceutical Sciences, Kanazawa University, Kakuma-machi, Kanazawa 920-1192, Japan.
authors.forename: I
authors.initials: I
authors.lastname: Tamai
authors.affiliation: Institute of Pharmacy, Johannes Gutenberg University, Staudingerweg 5, 55099 Mainz, Germany. Electronic address: langguth@uni-mainz.de.
authors.forename: P
authors.initials: P
authors.lastname: Langguth
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D000328:Adult; D032083:Citrus paradisi; D018592:Cross-Over Studies; D019587:Dietary Supplements; D004304:Dosage Forms; D004305:Dose-Response Relationship, Drug; D005260:Female; D044950:Flavanones / Q000008:administration & dosage* / Q000494:pharmacology; D018565:Food-Drug Interactions; D006801:Humans; D008297:Male; D027361:Organic Anion Transporters / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011412:Propanolamines / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D055815:Young Adult
chemical_list: D000319:Adrenergic beta-Antagonists; D004304:Dosage Forms; D044950:Flavanones; D027361:Organic Anion Transporters; D011412:Propanolamines; C011550:talinolol; C005274:naringin
keywords: Fruit juice; Interaction; Naringin; Nutraceutical; OATP; Talinolol