AMPRENAVIR/LOPINAVIR/RITONAVIR IN HIV-INFECTED PATIENTS

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。一些研究已经证明了APV和LPV/r以及FPV和LPV/r之间的负相互作用。FPV +LPV/r之间的药物相互作用似乎比APV +LPV/r之间的相互作用更大。此外，还有一种观点认为，增加两种药物的剂量可以克服APV + LPV/r相互作用；然而，对于FPV + LPV/r，同样的策略并不成功。然而，我们小组最近完成的一项研究结果发现，APV（以Agenerase形式递送）血浆Cmin加LPV/r 533mg/133mg BID与Wire等人使用FPV（以lexeva形式递送）1400mg BID加LPV/r 533mg/133mg BID的结果相当。血浆APV和LPV药代动力学的交叉研究比较表明，FPV 1400mg + LPV/r 533mg/133mg BID与LPV/r 400mg/100mg BID相比具有生物等效的血浆LPV暴露，与APV 750mg + LPV 533mg/133mg BID相比具有相似的血浆APV暴露。由于APV和FPV联合LPV/r之间缺乏强有力的比较，我们建议进行开放标签研究，比较amprenavir前药（fosamprenavir； FPV）与母药（amprenavir； APV）在与LPV/r（有或没有EFV）联合给药时的药代动力学、安全性和有效性。

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. Several studies have documented negative interactions between APV and LPV/r and between FPV and LPV/r. The drug interaction for FPV + LPV/r appears to be greater in magnitude than the interaction between APV +LPV/r. In addition, there is the perception that the APV + LPV/r interaction can be overcome by increasing doses of both drugs; whereas, the same strategy is not successful for FPV + LPV/r. However, results from a recently completed study by our group, found that APV (delivered as Agenerase) plasma Cmin plus LPV/r 533mg/133mg BID was comparable to what has been reported by Wire et al. using FPV (delivered as Lexiva)1400mg BID plus LPV/r 533mg/133mg bid. Cross-study comparisons of plasma APV and LPV pharmacokinetics suggest that FPV 1400mg + LPV/r 533mg/133mg BID would deliver bioequivalent plasma LPV exposure compared to LPV/r 400mg/100mg BID and similar plasma APV exposure compared to APV 750mg + LPV 533mg/133mg BID. Since robust comparisons between APV and FPV in combination with LPV/r are lacking, we are proposing open-label study to compare the pharmacokinetics, safety, and efficacy of the prodrug of amprenavir (fosamprenavir; FPV) with the parent drug (amprenavir; APV) when both are coadminstered with LPV/r (with or without EFV).