奈非那韦在感染HIV-1的孕妇和非孕妇中的药代动力学。
Pharmacokinetics of nelfinavir in HIV-1-infected pregnant and nonpregnant women.
作者信息
Villani P, Floridia M, Pirillo M F, Cusato M, Tamburrini E, Cavaliere A F, Guaraldi G, Vanzini C, Molinari A, degli Antoni A, Regazzi M
机构信息
Department of Pharmacology, IRCCS Policlinico S. Matteo, Pavia, Italy.
出版信息
Br J Clin Pharmacol. 2006 Sep;62(3):309-15. doi: 10.1111/j.1365-2125.2006.02669.x.
AIMS
To compare steady-state nelfinavir (NFV) pharmacokinetics in pregnant and nonpregnant HIV-infected women.
METHODS
Twenty-five pregnant HIV-infected women were selected from an ongoing observational study evaluating the pharmacokinetics of antiretroviral agents during pregnancy. Twenty of them were in the third and five in the second trimester. Data for the control group of 21 HIV-infected nonpregnant women were taken from a previous multicentre pharmacokinetic trial. All the participating women achieved steady-state plasma concentrations while on a highly active antiretroviral therapy (HAART) regimen including NFV (1250 mg bid) and two nucleoside reverse transcriptase inhibitors (NRTIs). Blood samples for NFV measurement were collected predose (C(trough)) and at 0.5, 1, 2, 3, 4, 5, 6, 8 and 12 h post dose.
RESULTS
During the third trimester of pregnancy NFV AUC(0-12 h) median (range) values were 25.76 (12.61-42.74) microg h(-1) ml(-1), and were 32.49 (19.16-63.81) microg h(-1) ml(-1) in the control group [mean difference - 9.30 microg h(-1) ml(-1); 95% confidence interval (CI) -15.76, -2.83; P < 0.05). Median oral clearance (CL/F) was significantly higher in pregnant women than in the control group (48.5 l h(-1), range 29.3-99.1 l h(-1) vs. 38.5 l h(-1), range 19.6-65.2 l h(-1); mean difference 12.6 l h(-1); 95% CI 3.3, 21.9) but the difference disappeared when CL/F was adjusted for body weight. C(trough) was significantly (P < 0.01) lower in pregnant compared with nonpregnant women (median 0.8 microg ml(-1), range 0-2.6 microg ml(-1) vs. 1.5 microg ml(-1), range 0.5-4.9 microg ml(-1); mean difference -1.0 microg ml(-1); 95% CI -1.7, -0.31). The median elimination half-life of NFV observed during pregnancy was 3.7 h (range 1.4-6.6 h), compared with 5.2 (range 3.1-10.1 h) in the control group (mean difference -1.7; 95% CI -2.8, -0.51).
CONCLUSIONS
Our results indicate that women in the later stages of pregnancy may be exposed to subtherapeutic concentrations of NFV. Thus, adjustments in drug dosage or frequency of administration may be required.
目的
比较怀孕和未怀孕的HIV感染女性中奈非那韦（NFV）的稳态药代动力学。
方法
从一项正在进行的观察性研究中选取25名怀孕的HIV感染女性，该研究评估孕期抗逆转录病毒药物的药代动力学。其中20名处于孕晚期，5名处于孕中期。21名未怀孕的HIV感染女性对照组的数据来自之前的一项多中心药代动力学试验。所有参与研究的女性在接受包括NFV（1250mg，每日两次）和两种核苷类逆转录酶抑制剂（NRTIs）的高效抗逆转录病毒治疗（HAART）方案时达到稳态血药浓度。在给药前（C（谷值））以及给药后0.5、1、2、3、4、5、6、8和12小时采集血样用于检测NFV。
结果
在孕晚期，NFV的AUC（0 - 12小时）中位数（范围）值为25.76（12.61 - 42.74）μg·h⁻¹·ml⁻¹，对照组为32.49（19.16 - 63.81）μg·h⁻¹·ml⁻¹[平均差值 - 9.30μg·h⁻¹·ml⁻¹；95%置信区间（CI）-15.76，-2.83；P < 0.05]。孕妇的口服清除率（CL/F）中位数显著高于对照组（48.5 l·h⁻¹，范围29.3 - 99.1 l·h⁻¹ 对比 38.5 l·h⁻¹，范围19.6 - 65.2 l·h⁻¹；平均差值12.6 l·h⁻¹；95% CI 3.3，21.9），但当CL/F根据体重进行调整时，差异消失。与未怀孕女性相比，孕妇的C（谷值）显著更低（P < 0.01）（中位数0.8μg·ml⁻¹，范围0 - 2.6μg·ml⁻¹ 对比 1.5μg·ml⁻¹，范围0.5 - 4.9μg·ml⁻¹；平均差值 -1.0μg·ml⁻¹；95% CI -1.7，-0.31）。孕期观察到的NFV消除半衰期中位数为3.7小时（范围1.4 - 6.6小时），对照组为5.2小时（范围3.1 - 10.1小时）（平均差值 -1.7；95% CI -2.8，-0.51）。
结论
我们的结果表明，怀孕后期的女性可能暴露于低于治疗浓度的NFV。因此，可能需要调整药物剂量或给药频率。
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