ACTG A5223: SEX DIFFERENCES IN LOPINAVIR/RITONAVIR PHARMACOKINETICS

这个子项目是许多利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 这项研究假设，女性达到更高的洛匹那韦（LPV）药物水平比男性在类似剂量的LPV和利托那韦（RTV）。 主要目的是比较目前接受相似剂量LPV/RTV的HIV-1感染男性和女性之间LPV的药代动力学（PK）参数、浓度-时间曲线下面积（AUC）。 将对78例可评价受试者（39例男性和39例女性）在早晨LPV/RTV给药前和给药后12小时内采集的血浆样本进行PK评价，这些受试者目前接受LPV/RTV作为抗逆转录病毒治疗方案的一部分。 筛选访视将在PK访视前30天内进行。 在确认合格性后，受试者将返回进行登记/入组访视以入组研究，并将获得一份48小时药物日志以完成。 要求受试者在GCRC接受约13小时的密集PK血样采集。 受试者将> 18岁并且目前接受LPV/RTV（洛匹那韦400 mg/利托那韦100 mg po bid）加以下一种或多种：核苷逆转录酶抑制剂（NRTI）、替诺福韦（核苷酸RTI）和恩夫韦肽（融合抑制剂）。 受试者必须在筛选前接受相同的方案至少14天。 受试者将按人种/种族分层。 这项研究可能会增加男性研究结果的效力和普遍性;初步研究表明，女性的PK、副作用和治疗效果存在差异。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This study hypothesizes that women achieve higher lopinavir (LPV) drug levels than do men on similar doses of LPV and ritonavir (RTV). The primary objective is to compare the pharmacokinetic (PK) parameter, area under the concentration-time curve (AUC) of LPV between HIV-1-infected men and women currently receiving similar doses of LPV/RTV. PK evaluations will be performed on plasma samples obtained prior to and up to 12 hours after the administration of the morning dose of LPV/RTV in 78 evaluable subjects (39 men and 39 women) currently managed on LPV/RTV as part of their antiretroviral regimen. A screening visit will occur within 30 days prior to the PK visit. Upon confirmation of eligibility, subjects will return for a registration/entry visit to enroll into the study and will be given a 48-hour medication diary to complete. Subjects will be required to spend approximately 13 hours at the GCRC for the intensive PK blood sampling. Subjects will be > 18 years old and currently receiving LPV/RTV (lopinavir 400 mg/ritonavir 100 mg po bid) plus one or more of the following: nucleoside reverse transcriptase inhibitors (NRTIs), tenofovir (a nucleotide RTI), and enfuvirtide (a fusion inhibitor). Subjects must be on the same regimen for at least 14 days prior to screening. Subjects will be stratified by race/ethnicity. This study may lead to increased power and generalizability of findings in men; preliminary studies suggest differences in PK, side effects, and therapeutic effects in women.