HIV/AIDS Research Department, Irmandade da Santa Casa de Misericordia de Porto Alegre, RS, Brazil.
J Acquir Immune Defic Syndr. 2013 May 1;63(1):59-66. doi: 10.1097/QAI.0b013e318289b4d2.
Reduced atazanavir exposure has been demonstrated during pregnancy with standard atazanavir/ritonavir dosing. We studied an increased dose during the third trimester of pregnancy.
International Maternal Pediatric Adolescent AIDS Clinical Trials Group 1026s is a prospective, nonblinded, pharmacokinetic study of HIV-infected pregnant women taking antiretrovirals for clinical indications, including 2 cohorts (with or without tenofovir) receiving atazanavir/ritonavir 300/100 mg once daily during the second trimester, 400/100 mg during the third trimester, and 300/100 mg postpartum (PP). Intensive steady-state 24-hour pharmacokinetic profiles were performed. Atazanavir concentrations were measured by high-performance liquid chromatography. Pharmacokinetic targets were the 10th percentile atazanavir area under the concentration versus time curve (AUC) (29.4 μg·hr·mL·) in nonpregnant adults on standard dose and 0.15 μg/mL, minimum trough concentration.
Atazanavir pharmacokinetic data were available for 37 women without tenofovir, 35 with tenofovir; median (range) pharmacokinetic parameters are presented for second trimester, third trimester, and PP and number who met target/total. ATAZANAVIR WITHOUT TENOFOVIR: AUC 30.5 (9.19-93.8), 45.7 (11-88.3), and 48.8 (9.9-112.2) μg·hr·mL, and 8/14, 29/37, and 27/34 met target. C24 h was 0.49 (0.09-4.09), 0.71 (0.14-2.09), and 0.90 (0.05-2.73) μg/mL; 13/14, 36/37, and 29/34 met target. ATAZANAVIR WITH TENOFOVIR: AUC 26.2 (6.8-60.9) (P < 0.05 compared with PP), 37.7 (0.72-88.2) (P < 0.05 compared with PP), and 58.6 (6-149) μg·hr·mL, and 7/17, 23/32, and 27/29 met target. C24 h was 0.44 (0.12-1.06) (P < 0.05 compared with PP), 0.57 (0.02-2.06) (P < 0.05 compared with PP), and 1.26 (0.09-5.43) μg/mL; 7/17, 23/32, and 27/29 met target. Atazanavir/ritonavir was well tolerated with no unanticipated adverse events.
Atazanavir/ritonavir increased to 400/100 mg provides adequate atazanavir exposure during the third trimester and should be considered during the second trimester.
标准剂量的阿扎那韦/利托那韦在妊娠期间会导致阿扎那韦暴露减少。我们研究了在妊娠晚期增加剂量。
国际母婴儿科青少年艾滋病临床试验组 1026s 是一项前瞻性、非盲、药代动力学研究，纳入了接受抗逆转录病毒药物治疗的 HIV 感染孕妇，包括两个队列（有或没有替诺福韦），在妊娠中期接受阿扎那韦/利托那韦 300/100mg 每日一次，在妊娠晚期接受 400/100mg，在产后接受 300/100mg。进行了强化稳态 24 小时药代动力学研究。阿扎那韦浓度通过高效液相色谱法进行测定。药代动力学目标是在标准剂量下非妊娠成人第 10 百分位数的阿扎那韦 AUC（29.4μg·hr·mL·）和 0.15μg/mL 的最小谷浓度。
37 名无替诺福韦的妇女和 35 名有替诺福韦的妇女有阿扎那韦药代动力学数据；给出了妊娠中期、妊娠晚期和产后的中位数（范围）药代动力学参数和达到目标的人数/总人数。无替诺福韦的阿扎那韦：AUC 30.5（9.19-93.8）、45.7（11-88.3）和 48.8（9.9-112.2）μg·hr·mL，8/14、29/37 和 27/34 达到目标。C24 h 为 0.49（0.09-4.09）、0.71（0.14-2.09）和 0.90（0.05-2.73）μg/mL；13/14、36/37 和 29/34 达到目标。有替诺福韦的阿扎那韦：AUC 26.2（6.8-60.9）（与产后相比，P<0.05）、37.7（0.72-88.2）（与产后相比，P<0.05）和 58.6（6-149）μg·hr·mL，7/17、23/32 和 27/29 达到目标。C24 h 为 0.44（0.12-1.06）（与产后相比，P<0.05）、0.57（0.02-2.06）（与产后相比，P<0.05）和 1.26（0.09-5.43）μg/mL；7/17、23/32 和 27/29 达到目标。阿扎那韦/利托那韦耐受性良好，无意外不良事件。
阿扎那韦/利托那韦增加至 400/100mg 可在妊娠晚期提供足够的阿扎那韦暴露，应在妊娠中期考虑使用。
