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. (1st February 2017)

• Record Type: Journal Article
• Authors: Yang, Wanqiu; Xiao, Qingqing; Wang, Dan; Yao, Cheng; Yang, Jin
• Is Part Of: Xenobiotica. Volume 47:Number 2(2017)
• Page Start: 133
• Page End: 143
• Publication Date: 2017-02-01
• Subjects: Albuvirtide -- drug-drug interaction -- HIV-1 -- lopinavir/ritonavir -- population pharmacokinetic model; Metabolism -- Periodicals; Drugs -- Physiological effect -- Periodicals; Food additives -- Periodicals; Chemicals -- Physiological effect -- Periodicals; Biochemistry -- Periodicals; Pharmaceutical Preparations -- metabolism -- Periodicals; Metabolism -- Periodicals; 574.133
• DOI: 10.3109/00498254.2016.1166532
• Languages: English
• ISSNs: 0049-8254

Abstract

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 ( C end ) 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 C trough [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 ), C max and C trough were 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.