Suvarna Vasanti M, Sangave Preeti C
Department of Pharmaceutical Chemistry and Quality Assurance, SVKM's Dr. Bhanuben Nanavati College of Pharmacy, V.L. Mehta Road, Vile Parle (West), Mumbai 400056, Maharashtra, India.
Department of Pharmaceutical Sciences, School of Pharmacy and Technology Management, SVKM's NMIMS, Mukesh Patel Technology Park, Bank of Tapi River, Mumbai-Agra Road, Shirpur 425405, Maharashtra, India.
J Chromatogr Sci. 2018 Apr 1;56(4):307-316. doi: 10.1093/chromsci/bmx113.
Darunavir ethanolate (DRV) is an efficient protease inhibitor (PI) used in the treatment of human immunodeficiency virus (HIV) type-1 patients. An isocratic reversed-phase HPLC method was developed to monitor concentration of darunavir in in vitro intestinal fluid samples in everted sac absorption model in the presence of bioenhancers, viz., piperine, quercetin, naringenin. The method was validated and successfully applied to everted sac and pharmacokinetic studies in rats. The absorption profiles of DRV and apparent permeability coefficients were determined. The proposed method was found to be simple, rapid, robust and selective and was applied for continuous ex vivo monitoring of DRV in everted sac absorption studies. Of the three bioenhancers screened at different concentrations, piperine caused highest and significant 1.5-fold increase in apparent permeability of DRV across everted sac tissue. Further, co-administration of piperine significantly increased the maximum plasma concentration of DRV by 1.18-fold confirming the enhancement in its absorption.
达芦那韦乙醇酸盐（DRV）是一种用于治疗1型人类免疫缺陷病毒（HIV）患者的高效蛋白酶抑制剂（PI）。开发了一种等度反相高效液相色谱法，用于在存在生物增强剂（即胡椒碱、槲皮素、柚皮素）的情况下，监测外翻肠囊吸收模型中体外肠液样本中的达芦那韦浓度。该方法经过验证，并成功应用于大鼠的外翻肠囊和药代动力学研究。测定了DRV的吸收曲线和表观渗透系数。所提出的方法被发现简单、快速、稳健且具有选择性，并应用于外翻肠囊吸收研究中DRV的连续离体监测。在不同浓度筛选的三种生物增强剂中，胡椒碱使DRV在外翻肠囊组织中的表观渗透率最高且显著增加了1.5倍。此外，胡椒碱的共同给药使DRV的最大血浆浓度显著增加了1.18倍，证实了其吸收的增强。
