Laboratory for Antiviral Research, Departments of Pharmacy Practice and Medicine, Schools of Pharmacy and Pharmaceutical Sciences and Medicine and Biomedical Sciences, University at Buffalo, 317 Hochstetter Hall, Buffalo, New York, 14260, USA.
Clin Drug Investig. 2002;22(2):125-34. doi: 10.2165/00044011-200222020-00007.
To characterise the pharmacokinetics of indinavir during different phases of the menstrual cycle in HIV-infected women.
Open-label study.
The immunodeficiency clinic at Erie County Medical Center, Buffalo, New York.
Ten HIV-infected women were enrolled in the study. Eligibility criteria included an acceptable medical history, chemistry profile, complete blood count with differential, lymphocyte profile, urinalysis and history of a regular menstrual cycle. PATIENTS had to be on a stable antiretroviral regimen that included indinavir 800mg taken every 8 hours.
Blood sampling over an 8-hour period following an 800mg dose of indinavir during the menstrual, follicular and luteal phases of the menstrual cycle.
Pharmacokinetic parameters in ten HIV-infected women adherent with indinavir 800mg every 8 hours during the menstrual, follicular and luteal phases of the menstrual cycle. Serum estradiol and progesterone levels were also obtained during each menstrual cycle phase.
The peak plasma concentration, plasma concentration 8 hours after administration of a given dose of indinavir, elimination half-life and oral clearance of indinavir were not significantly different across the menstrual cycle phases. Indinavir exposure varied among the female patients with some individuals having similar areas under the concentration-time curve (AUCs) during the three phases while others had notable differences in AUC. Maximum plasma indinavir concentrations were highest during the follicular phase in four subjects, highest during the luteal phase in two individuals, and highest during the menstrual phase in three patients.
No differences were found in indinavir pharmacokinetics during the menstrual cycle phases. Significant intra- and interpatient variability in indinavir pharmacokinetics were observed; however, indinavir exposure in women did not appear to be excessive compared with pharmacokinetic data obtained from prior studies conducted in men.
描述感染 HIV 的女性在月经周期不同阶段使用依地那韦的药代动力学特征。
开放标签研究。
纽约州布法罗市伊利县医疗中心的免疫缺陷诊所。
10 名 HIV 感染女性参与了该研究。入选标准包括可接受的病史、化学特征、全血细胞计数和分类、淋巴细胞谱、尿液分析以及月经周期史。患者必须接受稳定的抗逆转录病毒治疗方案，方案包括每 8 小时服用 800mg 依地那韦。
在月经周期的卵泡期和黄体期，患者服用 800mg 依地那韦后 8 小时内进行 8 小时的血样采集。
10 名依从性良好的 HIV 感染女性在月经周期的卵泡期和黄体期接受每 8 小时服用 800mg 依地那韦时的药代动力学参数。在每个月经周期阶段还获得了血清雌二醇和孕酮水平。
依地那韦的达峰血浆浓度、给药后 8 小时的血浆浓度、消除半衰期和口服清除率在月经周期各阶段均无显著差异。依地那韦的暴露量在女性患者中存在差异，部分个体在 3 个阶段的曲线下面积（AUC）相似，而其他个体的 AUC 差异显著。4 名患者的最大血浆依地那韦浓度在卵泡期最高，2 名患者在黄体期最高，3 名患者在月经期最高。
在月经周期各阶段，依地那韦的药代动力学无差异。观察到依地那韦药代动力学的显著个体内和个体间变异性；然而，与男性患者的药代动力学数据相比，女性患者的依地那韦暴露量似乎并未过高。
