Effects of valproic acid coadministration on plasma efavirenz and lopinavir concentrations in human immunodeficiency virus-infected adults
Effects of valproic acid coadministration on plasma efavirenz and lopinavir concentrations in human immunodeficiency virus-infected adults
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DOI：
10.1128/aac.48.11.4328-4331.2004
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发表时间：
2004-11-01
影响因子：
4.9
通讯作者：
Schifitto, G
中科院分区：
文献类型：
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作者：
DiCenzo, R;Peterson, D;Schifitto, G
丙戊酸（VPA）有可能使人类免疫缺陷病毒（HIV）相关认知障碍患者获益。本研究的目的是确定VPA是否影响依法韦仑（EFV）或洛匹那韦的血浆浓度。接受EFV或洛匹那韦-利托那韦（LPV/r）治疗的HIV 1型（HIV-1）感染患者在接受250 mg VPA每日两次持续7天之前和之后的稳态给药间隔8至24小时内采集9或10份血样。之前采集的VPA血样（C.）早晨给药后8小时（8小时）的血液样本与一组HIV-1感染受试者的血液样本进行比较，这些受试者单独服用联合核苷逆转录酶抑制剂或已停止抗逆转录病毒治疗。通过非房室分析计算药代动力学参数，生物等效性检验基于比值或差异的90%置信区间（CI）。EFV（n = 11）联合和不联合VPA的0 - 24 h浓度-时间曲线下面积（AUC（0-24）s）的几何均值比（GMR）（90% CI）为1.00（0.85，1.17）。联合和不联合VPA的LPV（n = 8）AUC（0-8）s的GMR（90% CI）为1.38（0.98，1.94）。平均C（0）和8小时VPA浓度与对照组（n = 11）的差异（90% CI）为-1.0 EFV（n = 10）和LPV/r（n = 11）分别为-5.0（-13.2，3.3）和-6.7（-17.6，4.2）μ g/ml。EFV单独给药与EFV和VPA联合给药生物等效。当药物与VPA联合使用时，LPV浓度往往更高。VPA比较结果未引起与EFV或LPV/r联合给药会显著影响VPA谷浓度的担忧。
Valproic acid (VPA) has the potential to benefit patients suffering from human immunodeficiency virus (HIV)-associated cognitive impairment. The purpose of this study was to determine if VPA affects the plasma concentration of efavirenz (EFV) or lopinavir. HIV type 1 (HIV-1)-infected patients receiving EFV or lopinavir-ritonavir (LPV/r) had 9 or 10 blood samples drawn over 8 to 24 h of a dosing interval at steady state before and after receiving 250 mg of VPA twice daily for 7 days. VPA blood samples drawn before (C.) and 8 h after the morning dose (8 h) were compared to blood samples from a group of HIV-1-infected subjects who were taking either combined nucleoside reverse transcriptase inhibitors alone or had discontinued antiretroviral therapy. Pharmacokinetic parameters were calculated by noncompartmental analysis, and tests of bioequivalence were based on 90% confidence intervals (CIs) for ratios or differences. The geometric mean ratio (GMR) (90% CI) of the areas under the concentration-time curve from 0 to 24 h (AUC(0-24)s) of EFV (n = 11) with and without VPA was 1.00 (0.85, 1.17). The GMR (90% CI) of the AUC(0-8)s of LPV (n = 8) with and without VPA was 1.38 (0.98, 1.94). The differences (90% CI) in mean C(0) and 8-h VPA concentrations versus the control (n = 11) were -1.0 (-9.4, 7.4) mug/ml and -2.1 (-11.1, 6.9) mug/ml for EFV (n = 10) and -5.0 (-13.2, 3.3) mug/ml and -6.7 (-17.6, 4.2) mug/ml for LPV/r (n = 11), respectively. EFV administration alone is bioequivalent to EFV and VPA coadministration. LPV concentrations tended to be higher when the drug was combined with VPA. Results of VPA comparisons fail to raise concern that coadministration with EFV or LPV/r will significantly influence trough concentrations of VPA.