Lopinavir/ritonavir reduces bupropion plasma concentrations in healthy subjects
Lopinavir/ritonavir reduces bupropion plasma concentrations in healthy subjects
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DOI：
10.1038/sj.clpt.6100027
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发表时间：
2007-01-01
影响因子：
6.7
通讯作者：
Lindley, C. M.
中科院分区：
文献类型：
--
作者：
Hogeland, G. W.;Swindells, S.;Lindley, C. M.
关于稳态洛匹那韦和利托那韦（LPV/r）对安非他酮药代动力学影响的数据有限。由于联合使用这两种药物可能会使患者受益，因此本研究确定了这种药物相互作用的程度和方向。12名健康志愿者在接受LPV/r 400 mg/100 mg每日2次治疗2周之前和之后接受单次100 mg缓释安非他酮给药。在第1天和第30天测定安非他酮和羟基安非他酮的药代动力学特征，在第29天和第30天测定LPV/r的药代动力学特征。LPV/r给药使安非他酮最大血药浓度（C-max）显著降低57%（90%置信区间（CI），38-76%; P < 0.01），曲线下面积（AUC）无穷大降低57%（90% CI，32-83%; P < 0.01）。羟基安非他酮C-max和AUC infinity分别降低31%（90% CI，7-55%; P < 0.01）和50%（90% CI，34-65%; P < 0.01）。单剂量安非他酮给药后，未发现LPV/r的药代动力学发生显著变化。同时使用LPV/r和安非他酮导致安非他酮及其活性代谢产物羟基安非他酮的暴露量降低，可能需要将安非他酮的剂量增加100%。这种相互作用的可能机制是细胞色素P450 2B 6和UDP-葡萄糖醛酸转移酶的同时诱导。LPV/r暴露不受单剂量安非他酮的影响。
Limited data are available about the effect of steady-state lopinavir and ritonavir (LPV/r) on bupropion pharmacokinetics. As patients may benefit by using these two agents in combination, this study determined the extent and direction of this drug-drug interaction. Twelve healthy volunteers received a single 100 mg dose of sustained-release bupropion before and after 2 weeks of treatment with LPV/r 400 mg/100 mg twice daily. Pharmacokinetics profiles were determined on days I and 30 for bupropion and hydroxybupropion and days 29 and 30 for LPV/r. LPV/r administration significantly decreased bupropion maximum plasma concentration (C-max) by 57% (90% confidence interval (CI), 38-76%; P < 0.01) and area under the curve (AUC)infinity by 57% (90% CI, 32-83%; P < 0.01). Hydroxybupropion C-max and AUC infinity decreased by 31% (90% CI, 7-55%; P < 0.01) and by 50% (90% CI, 34-65%; P < 0.01), respectively. No significant changes in the pharmacokinetics of LPV/r were found following administration of a single dose of bupropion. Concurrent use of LPV/r and bupropion resulted in decreased exposure to bupropion and its active metabolite hydroxybupropion that may necessitate as much as a 100% dose increase of bupropion. A probable mechanism for this interaction is the concurrent induction of cytochrome P450 2B6 and UDP-glucuronosyltransferase enzymes. LPV/r exposure is unaffected by a single dose of bupropion.