Effects of clarithromycin and grapefruit juice on the pharmacokinetics of glibenclamide.
Effects of clarithromycin and grapefruit juice on the pharmacokinetics of glibenclamide.
复制标题
克拉霉素和柚子汁对格列本脲药代动力学的影响。
DOI：
--
复制
发表时间：
2007
影响因子：
3.4
通讯作者：
P. Neuvonen
中科院分区：
文献类型：
--
作者：
J. Lilja;M. Niemi;H. Fredrikson;P. Neuvonen
目标
病例报道提示，克拉霉素可增强格列本脲的降糖作用，格列本脲主要由细胞色素P450代谢，是P-糖蛋白和OATP2B1的底物。我们的目的是评估P-糖蛋白抑制剂克拉霉素是否能增加格列本脲的血药浓度，而可能的OATP2B1抑制剂西柚汁能降低格列本脲的血浆浓度。
方法
在一项随机的三阶段交叉研究中，12名受试者每天两次服用250毫克克拉霉素或安慰剂，或每天三次服用200毫升西柚汁，为期两天。第三天，他们摄入0.875毫克格列本脲和糖水或西柚汁。测定12h内格列本脲和克拉霉素的血药浓度、血糖和尿中羟基格列本脲的排泄量。
结果
与安慰剂相比，克拉霉素使格列本脲的峰值浓度(C(Max))增加到1.25倍(95%可信区间(CI)1.12，1.40；P<；0.01)，血药浓度-时间曲线下面积增加到1.35倍(95%CI 1.21，1.50；P<；0.01)。达到C(Max)的时间、格列本脲的半衰期和排入尿中的羟基格列本脲的量保持不变。西柚汁不改变格列本脲的药代动力学。克拉霉素浓度表明依从性良好。血糖在各时相之间没有偏离。
结论
克拉霉素增加格列本脲的血浆浓度，可能是通过抑制肠壁的P-糖蛋白。虽然在目前的研究设计中看不到克拉霉素，但克拉霉素可能通过增加格列本脲的血浆浓度来增强格列本脲的疗效，这需要在联合给药期间密切监测血糖。西柚汁对格列本脲的药代动力学无影响。
AIMS
Case reports suggest that clarithromycin can increase the glucose-lowering effect of glibenclamide which is metabolized mainly by CYP2C9 and is a substrate for P-glycoprotein and OATP2B1. Our objective was to evaluate whether the P-glycoprotein inhibitor, clarithromycin, increases and the putative OATP2B1 inhibitor, grapefruit juice, decreases plasma concentrations of glibenclamide.
METHODS
In a randomized three-phase crossover study, 12 subjects ingested 250 mg clarithromycin or placebo twice daily or 200 ml grapefruit juice three times daily for 2 days. On day 3, they ingested 0.875 mg glibenclamide with sugar water or grapefruit juice. Concentrations of glibenclamide and clarithromycin in plasma, glucose in blood, and excretion of hydroxy-glibenclamide into urine were measured up to 12 h.
RESULTS
Clarithromycin increased the peak concentration (C(max)) of glibenclamide to 1.25-fold (95% confidence interval (CI) 1.12, 1.40; P < 0.01) and the area under the plasma concentration-time curve to 1.35-fold (95% CI 1.21, 1.50; P < 0.01) compared with the placebo phase. The time to C(max), the half-life of glibenclamide, and the amount of hydroxy-glibenclamide excreted into urine remained unaltered. Grapefruit juice did not change the pharmacokinetics of glibenclamide. Clarithromycin concentrations implied a good compliance. Blood glucose did not deviate between the phases.
CONCLUSIONS
Clarithromycin increased plasma concentrations of glibenclamide, possibly by inhibiting P-glycoprotein in the intestinal wall. Although not seen with the present study design, clarithromycin may enhance the effect of glibenclamide by increasing plasma glibenclamide concentrations, which warrants close monitoring of blood glucose during their co-administration. Grapefruit juice had no effect on glibenclamide pharmacokinetics.
影响因子：
15.9
作者：
Lown, KS;Bailey, DG;Watkins, PB
通讯作者：
Watkins, PB
DOI：
--
发表时间：
2001-07
期刊：
Drug metabolism and disposition: the biological fate of chemicals
影响因子：
--
作者：
M. Bruce;S. Hall;B. Haehner‐Daniels;J. Gorski
通讯作者：
M. Bruce;S. Hall;B. Haehner‐Daniels;J. Gorski