Ripamonti Diego, Cattaneo Dario, Maggiolo Franco, Airoldi Monica, Frigerio Luigi, Bertuletti Pierangelo, Ruggeri Maurizio, Suter Fredy
Division of Infectious Diseases, Ospedali Riuniti, Bergamo, Italy.
AIDS. 2007 Nov 30;21(18):2409-15. doi: 10.1097/QAD.0b013e32825a69d1.
Adequate antiretroviral exposure during pregnancy is critical to prevent the vertical transmission of HIV and for maternal health. Pregnancy can alter drug kinetics. We assessed the pharmacokinetics of atazanavir/ritonavir (300/100 mg a day) during pregnancy.
An intensive steady-state 24-h pharmacokinetic profile of atazanavir was performed in the third trimester of pregnancy and postpartum. Maternal and umbilical cord blood samples were obtained at delivery. We measured atazanavir by reverse-phase high-performance liquid chromatography.
Seventeen women completed the study. Antepartum, the atazanavir geometric mean area under the plasma concentration-time curve from 0 to 24 h (AUC0-24) was 28 510 ng.h/l, the maximum observed plasma concentration (Cmax) was 2 591 ng/ml and the 24-h postdose concentration (Ctrough) was 486 ng/ml. The same postpartum parameters were 30 465 ng.h/l, 2 878 ng/ml and 514 ng/ml, respectively. The antepartum to postpartum ratio for AUC0-24 was 0.94 and for Ctrough was 0.96, indicating equivalence, whereas Cmax values were slightly although not significantly lower. The ratio of cord blood/maternal atazanavir concentration in 14 paired samples was 0.13.
Atazanavir exposure during the third trimester of pregnancy is similar to that observed in the non-pregnant period. Over the whole dosing interval, therapeutic drug concentrations well above the wild-type HIV 90% inhibitory concentration are maintained. Atazanavir crosses the placenta, potentially providing further protection for the newborn. As pregnancy does not appear to alter atazanavir exposure, no dose adjustment is required in pregnant women. Results suggest that atazanavir is a reasonable component of HAART during pregnancy.
孕期充分的抗逆转录病毒药物暴露对于预防HIV垂直传播及保障母体健康至关重要。妊娠会改变药物动力学。我们评估了孕期阿扎那韦/利托那韦（每日300/100毫克）的药代动力学。
在妊娠晚期和产后进行了阿扎那韦强化稳态24小时药代动力学分析。分娩时采集母体和脐带血样本。我们采用反相高效液相色谱法测定阿扎那韦。
17名女性完成了研究。产前，阿扎那韦0至24小时血浆浓度-时间曲线下的几何平均面积（AUC0-24）为28510纳克·时/升，观察到的最大血浆浓度（Cmax）为2591纳克/毫升，给药后24小时浓度（Ctrough）为486纳克/毫升。产后相同参数分别为30465纳克·时/升、2878纳克/毫升和514纳克/毫升。AUC0-24的产前与产后比值为0.94，Ctrough的比值为0.96，表明二者相当，而Cmax值略低但无显著差异。14对配对样本中脐带血/母体阿扎那韦浓度比值为0.13。
妊娠晚期阿扎那韦的暴露情况与非孕期相似。在整个给药间隔期间，可维持远高于野生型HIV 90%抑制浓度的治疗药物浓度。阿扎那韦可穿过胎盘，可能为新生儿提供进一步保护。由于妊娠似乎未改变阿扎那韦的暴露情况，孕妇无需调整剂量。结果表明，阿扎那韦是孕期高效抗逆转录病毒治疗的合理组成部分。
