Formulation and pharmacology of long-acting cabotegravir.
Formulation and pharmacology of long-acting cabotegravir.
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DOI：
10.1097/coh.0000000000000168
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发表时间：
2015-07
影响因子：
4.1
通讯作者：
Piscitelli S
中科院分区：
文献类型：
--
作者：
Trezza C;Ford SL;Spreen W;Pan R;Piscitelli S
长效cabotegravir可能为治疗和预防HIV-1感染提供一种新的治疗选择，不需要坚持每日方案。本综述将突出长效cabotegravir纳米混悬液的独特制剂特性和药理学属性。Cabotegravir是一种有效的整合酶链转移抑制剂，已被配制为每日口服片剂和长效注射纳米混悬液。长效cabotegravir在肌内和皮下给药后易于吸收，消除半衰期约为40天，允许每月或更低频率的给药方案。重复给药药代动力学研究和群体药代动力学建模表明，每月一次和每两个月一次给药可达到临床相关的血浆浓度，被认为对HIV维持治疗有效，每季度一次注射适合作为暴露前预防进行研究。Cabotegravir主要通过尿苷二磷酸葡萄糖醛酸转移酶1A 1代谢，不太可能受到细胞色素P450代谢途径的影响。体外和体内数据表明，cabotegravir引起或发生显著药物相互作用的倾向较低。长效cabotegravir的药理学特征支持其继续开发用于治疗和预防HIV-1感染。
Long-acting cabotegravir may provide a novel therapeutic option for both the treatment and prevention of HIV-1 infection that does not necessitate adherence to a daily regimen. The present review will highlight the unique formulation properties and pharmacologic attributes of long-acting cabotegravir nanosuspension. Cabotegravir is a potent integrase strand transfer inhibitor that has been formulated as an oral tablet for daily administration and as a long-acting injectable nanosuspension. Long-acting cabotegravir is readily absorbed following intramuscular and subcutaneous administration and has an elimination half-life of approximately 40 days, allowing for administration on a monthly or less frequent schedule. Repeat-dose pharmacokinetic studies and population pharmacokinetic modeling indicate monthly and bi-monthly dosing achieves clinically relevant plasma concentrations considered effective for HIV maintenance therapy and that quarterly injections are appropriate for investigation as preexposure prophylaxis. Cabotegravir is primarily metabolized by uridine diphosphate glucuronosyltransferase 1A1 and is unlikely to be impacted by the cytochrome P450 metabolic pathway. In vitro and in vivo data suggest cabotegravir has a low propensity to cause, or be subject to, significant drug interactions. The pharmacologic profile of long-acting cabotegravir supports its continued development for both treatment and prevention of HIV-1 infection.