Grapefruit juice ingestion significantly reduces talinolol bioavailability.
Grapefruit juice ingestion significantly reduces talinolol bioavailability.
复制标题
摄入葡萄柚汁会显着降低他林洛尔的生物利用度。
DOI：
10.1016/j.clpt.2004.11.111
复制
发表时间：
2005
影响因子：
6.7
通讯作者：
Kirch,Wilhelm
中科院分区：
文献类型：
--
作者：
Schwarz,UteI;Seemann,Diana;Oertel,Reinhard;Miehlke,Stephan;Kuhlisch,Eberhard;Fromm,MartinF;Kim,RichardB;Bailey,DavidG;Kirch,Wilhelm
我们的目的是评估单次和多次摄入葡萄柚汁相对于水对非代谢和P糖蛋白转运药物他他洛尔在人体内的口服药代动力学的影响，并评估摄入葡萄柚汁对P糖蛋白和肠道摄取转运蛋白的潜在影响。方法对24名健康白人志愿者口服50 mg他他洛尔，分别与水、1杯西柚汁（300 mL）和连续饮用西柚汁（900 mL/d） 6 d后的药代动力学进行测定。在摄入西柚汁前后，对3名受试者的十二指肠活检标本进行mdr1信使核糖核酸和P糖蛋白水平的测量。还评估了themdr1基因中三种常见的多态性。结果单杯葡萄柚汁使他他洛尔在血药浓度-时间曲线下的面积（AUC）、血药峰浓度（Cmax）和尿排泄值分别比水组降低56% （P< 0.001）、57% （P< 0.001）和56% （P< 0.001）。重复饮用葡萄柚汁也有类似的效果（减少44%至65%；P< 0.01）。单次或重复饮用果汁不会影响肾脏清除率、消除半衰期或达到Cmax（tmax）的时间。十二指肠活检标本中的mdr1信使核糖核酸和P糖蛋白水平不受葡萄柚汁的影响。mdr1基因型（C1236T、G2677T/A和C3435T）与他替洛尔药代动力学改变无关。结论：由于单次和多次饮用葡萄柚汁都降低而不是增加了他他洛尔的AUC，我们的研究结果表明，葡萄柚汁中的成分优先抑制了肠道摄取过程，而不是P糖蛋白。此外，葡萄柚汁没有改变肠道P糖蛋白的表达。临床药理学与治疗学（2005）77,291-301；doi: 10.1016 / j.clpt.2004.11.111
ObjectivesOur 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.MethodsThe 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.MDR1messenger 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 theMDR1gene were also assessed.ResultsA 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).MDR1messenger ribonucleic acid and P‐glycoprotein levels in duodenal biopsy specimens were not affected by grapefruit juice.MDR1genotypes (C1236T, G2677T/A, and C3435T) were not associated with altered talinolol pharmacokinetics.ConclusionBecause 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.Clinical Pharmacology & Therapeutics(2005)77, 291–301; doi: 10.1016/j.clpt.2004.11.111