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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Grapefruit juice ingestion significantly reduces talinolol bioavailability.

OBJECTIVES: Our objectives were to evaluate the effect of single and repeated grapefruit juice ingestion relative to water on the oral pharmacokinetics of the nonmetabolized and P-glycoprotein-transported drug talinolol in humans and to assess the potential impact of grapefruit juice ingestion on P-glycoprotein and intestinal uptake transporters. METHODS: The oral pharmacokinetics of 50 mg talinolol was determined with water, with 1 glass of grapefruit juice (300 mL), and after 6 days of repeated grapefruit juice ingestion (900 mL/d) in 24 healthy white volunteers. MDR1 messenger ribonucleic acid and P-glycoprotein levels were measured in duodenal biopsy specimens obtained from 3 individuals before and after ingestion of grapefruit juice. Three commonly occurring polymorphisms in the MDR1 gene were also assessed. RESULTS: A single glass of grapefruit juice decreased the talinolol area under the serum concentration-time curve (AUC), peak serum drug concentration (Cmax), and urinary excretion values to 56% (P < .001), 57% (P < .001), and 56% (P < .001), respectively, of those with water. Repeated ingestion of grapefruit juice had a similar effect (44% to 65% reduction; P < .01). Single or repeated juice ingestion did not affect renal clearance, elimination half-life, or time to reach Cmax (tmax). MDR1 messenger ribonucleic acid and P-glycoprotein levels in duodenal biopsy specimens were not affected by grapefruit juice. MDR1 genotypes (C1236T, G2677T/A, and C3435T) were not associated with altered talinolol pharmacokinetics. CONCLUSION: Because both single and repeated ingestion of grapefruit juice lowered rather than increased talinolol AUC, our findings suggest that constituents in grapefruit juice preferentially inhibited an intestinal uptake process rather than P-glycoprotein. Moreover, grapefruit juice did not alter intestinal P-glycoprotein expression.[1]


  1. Grapefruit juice ingestion significantly reduces talinolol bioavailability. Schwarz, U.I., Seemann, D., Oertel, R., Miehlke, S., Kuhlisch, E., Fromm, M.F., Kim, R.B., Bailey, D.G., Kirch, W. Clin. Pharmacol. Ther. (2005) [Pubmed]
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