Fletcher C V, Brundage R C, Fenton T, Alvero C G, Powell C, Mofenson L M, Spector S A
Division of Infectious Diseases, Department of Pharmaceutical Sciences, University of Colorado Health Sciences Center, Denver, Colorado, USA.
Clin Pharmacol Ther. 2008 Feb;83(2):300-6. doi: 10.1038/sj.clpt.6100282. Epub 2007 Jul 4.
Fifty human immunodeficiency virus (HIV)-infected children participated in an area-under-the plasma concentration-time curve (AUC)-controlled trial of efavirenz and nelfinavir. Pharmacokinetic evaluations were performed at weeks 2, 6, and 56. Efavirenz and nelfinavir doses were adjusted to achieve AUC values of 60-120 and > or = 10 mg h/l, respectively. Thirty-seven (74%) children met the efavirenz target and 41 (82%) the nelfinavir by week 10. Children with AUC values for both drugs above the first quartile were more likely to reach < 400 copies/ml of HIV RNA at week 8. Efavirenz and nelfinavir oral clearance increased 37 and 62% from weeks 2 to 56, respectively, in 34 children who continued on therapy at week 56. AUC values at week 56 were not different between children who did or did not have HIV RNA < 400 copies/ml. Dose adjustment to achieve specific AUC values in these children reduced the risk of suboptimal exposure and achieved high rates of virologic suppression.
五十名感染人类免疫缺陷病毒（HIV）的儿童参与了一项依法韦仑和奈非那韦的血浆浓度-时间曲线下面积（AUC）对照试验。在第2周、第6周和第56周进行了药代动力学评估。依法韦仑和奈非那韦的剂量分别调整为达到60-120和≥10mg·h/l的AUC值。到第10周时，37名（74%）儿童达到了依法韦仑的目标，41名（82%）儿童达到了奈非那韦的目标。两种药物的AUC值均高于第一四分位数的儿童在第8周时更有可能使HIV RNA水平降至<400拷贝/ml。在第56周继续接受治疗的34名儿童中，依法韦仑和奈非那韦的口服清除率分别从第2周到第56周增加了37%和62%。HIV RNA水平<400拷贝/ml和≥400拷贝/ml的儿童在第56周时的AUC值并无差异。在这些儿童中调整剂量以达到特定的AUC值可降低暴露不足的风险，并实现较高的病毒学抑制率。
