ABT 378/RITONAVIR IN COMBINATION WITH REVERSE TRANSCRIPTASE INHIBITORS

M97-720方案是一项I/II期、随机、ABT-378剂量盲、多中心研究，ABT-378/利托那韦联合他夫定（d4T）和拉米夫定（3TC）在健康的hiv感染男性和女性中进行。ABT-378是一种新型的拟肽HIV蛋白酶抑制剂，其体内效力比利托那韦高约10倍。ABT-378在50%的人血清中的EC50约为0.1微米。与一组表现出不同程度利托那韦耐药性的病毒分离物相比，ABT-378表现出一贯优于利托那韦的活性。ABT-378与利托那韦联合用药可显著改善药物的药代动力学特征。本研究的主要目的是评估口服ABT-378/利托那韦在抗逆转录病毒初始hiv感染患者中的安全性、耐受性和抗病毒活性。该研究还将确定ABT-378/利托那韦的稳态药代动力学特征和HIV RNA衰变特征。

Protocol M97-720 is a Phase I/II, randomized, ABT-378 dose-blinded, multicenter study of ABT-378/ritonavir in combination with stavudine (d4T) and lamivudine (3TC) in otherwise healthy HIV-infected males and females. ABT-378 is a novel peptidomimetic HIV protease inhibitor with approximately 10-fold greater in vivo potency than ritonavir. The EC50 of ABT-378 in 50% human serum is approximately 0.1 micrometer. Against a panel of viral isolates demonstrating varying degrees of ritonavir resistance, ABT-378 demonstrated consistently superior activity compared with ritonavir. Co-administration of ABT-378 with ritonavir substantially improves the pharmacokinetic profile of the drug. The primary objective of this study is to assess the safety, tolerability, and antiviral activity of ABT-378/ritonavir when administered orally in antiretroviral naive HIV-infected patients. The study will also determine the steady-state pharmacokinetic profile and characterize HIV RNA decay profiles of ABT-378/ritonavir.