Effect of ritonavir on the pharmacokinetics of ethinyl oestradiol in healthy female volunteers
Effect of ritonavir on the pharmacokinetics of ethinyl oestradiol in healthy female volunteers
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DOI：
10.1046/j.1365-2125.1998.00749.x
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发表时间：
1998-08-01
影响因子：
3.4
通讯作者：
Granneman, GR
中科院分区：
文献类型：
--
作者：
Ouellet, D;Hsu, A;Granneman, GR
目的评估蛋白酶抑制剂利托那韦对炔雌醇在健康女性volunteers.Methods的药代动力学的影响，这是一个开放标签，单中心研究23名受试者谁收到两个单剂量的口服避孕药，含50微克炔雌醇在第1天（单独）和第29天，在伴随利托那韦。每例受试者从第15天至第30天接受利托那韦给药，每12小时给药一次，共16天。每次给药后48 h采集血样测定血清炔雌醇浓度，第29天给药后0 h和4 h采集血样测定血浆利托那韦浓度。伴随利托那韦给药期间，调和平均终末半衰期从17 h缩短至13 h。t（max）未观察到统计学显著性变化。C-max和AUC的均值比（95%置信区间）分别为0.682（0.612-0.758）和0.595（0.506-0.694）。炔雌醇药代动力学的变化与葡萄糖醛酸化和/或细胞色素P450羟基化酶诱导的清除率增加一致。平均稳态利托那韦浓度为6.5和13.4 μ g/ml（-1），观察到在0和4 h postdose，foreign.Conclusions考虑到炔雌醇浓度下降的程度，应考虑使用替代避孕措施时，利托那韦正在管理。
Aims To assess the effects of the protease inhibitor ritonavir on the pharmacokinetics of ethinyl oestradiol in healthy female volunteers.Methods This was an open-label, single centre study in 23 subjects who received two single doses of oral contraceptive containing 50 mu g ethinyl oestradiol on Day 1 (alone) and on Day 29 during concomitant ritonavir. Each subject received 16 days of every 12 h doses of ritonavir from Day 15 through Day 30. Blood samples were collected for serum ethinyl oestradiol concentrations for 48 h after each dose and for plasma ritonavir on Day 29 at 0 and 4 h postdose.Results Statistically significant decreases in ethinyl oestradiol mean C-max (-32%) and mean AUC (-41%), and a statistically significant increase in the mean terminal elimination rats constant (+31%) were observed during concomitant ritonavir. The harmonic mean terminal half-life decreased from 17 h to 13 h during concomitant ritonavir. No statistically significant change was noted in t(max). The ratios of means (95% confidence intervals) for C-max and AUC were 0.682 (0.612-0.758) and 0.595 (0.506-0.694), respectively. The changes in ethinyl oestradiol pharmacokinetics were consistent with an increase in clearance from enzymatic induction of glucuronidation and/or cytochrome P450 hydroxylation. Mean steady-state ritonavir concentrations of 6.5 and 13.4 mu g ml(-1) were observed at 0 and 4 h postdose, respectively.Conclusions Considering the extent of the decrease in ethinyl oestradiol concentrations, the use of alternate contraceptive measures should be considered when ritonavir is being administered.