title: Evaluation of pharmacokinetic interactions between long-acting HIV-1 fusion inhibitor albuvirtide and lopinavir/ritonavir, in HIV-infected subjects, combined with clinical study and simulation results.
abstract: 1. A clinical study to assess the interactions between albuvirtide (320 mg) and lopinavir/ritonavir (400/100 mg) was conducted in 10 HIV-1-infected subjects. Because albuvirtide requires a long period to achieve steady state, and extended monotherapy may lead to early resistance, it is unethical to take albuvirtide alone to achieve steady state. Therefore, a population pharmacokinetic model was developed to predict steady-state concentration-time curve of solely administered albuvirtide. 2. When albuvirtide and lopinavir/ritonavir were co-administered, the plasma concentration of albuvirtide when the infusion ended (Cend) increased by about 34%, but the geometric mean ratios and 90% confidence intervals (90% CIs) of AUC(0-t)[1.09 (0.96-1.24)] and Ctrough[1.00 (0.83-1.20)] were within the range of 0.8-1.25. For lopinavir, the ratios (90% CIs) of AUC(0-t), Cmaxand Ctroughwere 0.63 (0.49-0.82), 0.67 (0.53-0.86) and 0.65 (0.46-0.91); for ritonavir, those ratios (90% CIs) were 0.62 (0.42-0.91), 0.61 (0.38-0.99) and 0.72 (0.40-1.26), respectively. 3. Co-administration of albuvirtide with lopinavir/ritonavir has little effect on albuvirtide exposure, but it decreases the plasma exposures of lopinavir/ritonavir. However, the drug-drug interactions may not reduce the effectiveness of this co-therapy, the trough concentration of lopinavir may be sufficient and this combination could achieve similar clinical efficacy with marketed drugs. So, a phase 3 clinical trial without dose adjustment is underway to validate their effectiveness and safety.
authors.affiliation: a Center of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University , Nanjing , China.
authors.forename: Wanqiu
authors.initials: W
authors.lastname: Yang
authors.affiliation: b Department of Clinical Pharmacy , School of Pharmacy, China Pharmaceutical University , Nanjing , China , and.
authors.forename: Qingqing
authors.initials: Q
authors.lastname: Xiao
authors.affiliation: a Center of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University , Nanjing , China.
authors.forename: Dan
authors.initials: D
authors.lastname: Wang
authors.affiliation: c Nanjing Frontier Biotechnologies Co , Nanjing , China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Yao
authors.affiliation: a Center of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University , Nanjing , China.
authors.forename: Jin
authors.initials: J
authors.lastname: Yang
mesh_terms: D019380:Anti-HIV Agents / Q000493:pharmacokinetics*; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D015658:HIV Infections; D017320:HIV Protease Inhibitors; D015497:HIV-1; D006801:Humans; D061466:Lopinavir / Q000493:pharmacokinetics*; D008301:Maleimides / Q000493:pharmacokinetics*; D010455:Peptides / Q000493:pharmacokinetics*; D019438:Ritonavir / Q000493:pharmacokinetics*
chemical_list: D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D008301:Maleimides; D010455:Peptides; D061466:Lopinavir; C573334:albuvirtide; D019438:Ritonavir
keywords: Albuvirtide; HIV-1; drug-drug interaction; lopinavir/ritonavir; population pharmacokinetic model