依非韦伦的肝细胞毒性作用及对蛋白质表达谱的影响

目的 探讨依非韦伦对肝细胞的毒性作用及对蛋白质表达谱的影响.方法 人肝癌细胞系Huh7中分别加入依非韦伦1.25,2.5,5和10 mg·L-1,培养5h后采用原位比色法测定细胞内活性氧类(ROS)的含量;依非韦伦2.5mg·L-1与细胞作用5h后,用膜联蛋白-Ⅴ/碘化丙啶细胞凋亡检测试剂盒染色.用流式细胞仪测定细胞凋...     

Synergistic encapsulation of the anti-HIV agent efavirenz within mixed poloxamine/poloxamer polymeric micelles

This study investigated the synergistic performance of mixed polymeric micelles made of linear and branched poly(ethylene oxide)-poly(propylene oxide) for the more effective encapsulation of the anti-HIV drug efavirenz. The co-micellization process of 10% binary systems combining different weight ratios of a highly hydrophilic poloxamer (Pluronic F127) and a more hydrophobic poloxamine counterpart (Tetronic T304 and T904) was investigated by means of dynamic light scattering, cloud point and electronic spin resonance experiments. Then, the synergistic solubilization capacity of the micelles was shown. Findings revealed a sharp solubility increase from 4 μg/ml up to more than 33 mg/ml, representing a 8430-fold increase. Moreover, the drug-loaded mixed micelles displayed increased physical stability over time in comparison with pure poloxamine ones. Overall findings confirmed the enormous versatility of the poloxamer/poloxamine systems as Trojan nanocarriers for drug encapsulation and release by the oral route and they entail a relevant enhancement of the previous art towards a more compliant pediatric HIV pharmacotherapy.

From the Clinical Editor

In this study, the authors demonstrate the versatility of poloxamer/poloxamine systems as Trojan nanocarriers for anti-HIV drug encapsulation and release by the oral route. A highly relevant stability and solubility enhancement is shown, which may ultimately lead to more compliant anti-HIV pharmacotherapy.     

Role of Cytochrome P450 2B6 Pharmacogenomics in Determining Efavirenz‐Mediated Central Nervous System Toxicity,Treatment Outcomes,and Dosage Adjustments in Patients with Human Immunodeficiency Virus Infection

For treatment‐naive patients with human immunodeficiency virus infection, efavirenz (EFV), together with tenofovir and emtricitabine, was once widely prescribed given its efficacy and ease of administration in a combination pill. However, the high rate of central nervous system (CNS) toxicities from EFV prompted the U.S. Department of Health and Human Services to move the EFV‐based regimen from the recommended to the alternative category. For patients who do meet the criteria for newer recommended antiretroviral treatments, EFV is a viable option and often the mainstay of treatment outside the United States because newer antiretroviral treatments are more expensive. CNS toxicity occurring with the recommended standard dose of EFV remains a challenge and may in part be attributable to polymorphisms in cytochrome P450 (CYP) 2B6, the enzyme involved in the major metabolic pathway for converting EFV to inactive metabolites. Functionally deficient alleles of CYP2B6 such as CYP2B6*6, *18, and *22 may be responsible for significantly higher therapeutic concentrations of EFV at a standard dose of 600 mg/day. We conducted a thorough review of the reported studies to elucidate the relationship between polymorphisms in CYP2B6 with adverse events and treatment response, including virologic suppression, immunologic response, resistance, and discontinuation of treatment. Compelling evidence exists to support the case for CYP2B6 genotype–guided EFV therapy while acknowledging the need for prospective controlled clinical trials to evaluate its clinical utility.     

中药益艾康与HAART药物依非韦伦片相互作用研究

目的：探讨益艾康胶囊与HAART药物依非韦伦的相互作用。 方法：实验大鼠分别灌胃给予依非韦伦和依非韦伦+益艾康胶囊,并通过LC/MS/MS测定两种给药方式后血浆中依非韦伦浓度,随后使用Phoenix WinNonlin 6.1软件计算药动学参数。结果：符合方法学考察要求：血药浓度在5-500ng·mL-¹范围内线性关系良好,日内、日间精密度RSD均小于10.0%、提取回收率97.0%-104.0%、稳定性较好、受基质影响较小。由两组药代动力学主要参数得知AUC_（0-t）、AUC_（0-∞）、MRT_（0-t）和MRT_（0-∞）均显著降低（P<0.05）,其它参数无统计学意义（P>0.05）。结论：中药益艾康可能对依非韦伦在大鼠体内药代动力学行为有一定的影响,两者在临床上是否存在相互作用需要进一步研究。