Bart Gavin, Jaber Mutaz, Giang Le Minh, Brundage Richard C, Korthuis P Todd
Department of Medicine, Hennepin Healthcare, 701 Park Avenue, Minneapolis, MN 55415, USA.
Department of Experimental and Clinical Pharmacology, University of Minnesota College of Pharmacy, 417 Delaware Street SE, Minneapolis, MN 55455, USA.
Drug Alcohol Depend. 2022 Dec 1;241:109696. doi: 10.1016/j.drugalcdep.2022.109696. Epub 2022 Nov 11.
Buprenorphine is widely used in the treatment of opioid use disorder (OUD). There are few pharmacokinetic models of buprenorphine across diverse populations. Population pharmacokinetics (POPPK) allows for covariates to be included in pharmacokinetic studies, thereby opening the potential to evaluate the effect of comorbidities, medications, and other factors on buprenorphine pharmacokinetics. This pilot study used POPPK to explore buprenorphine pharmacokinetics in patients with and without HIV receiving buprenorphine for OUD.
Plasma buprenorphine levels were measured in 54 patients receiving buprenorphine for OUD just prior to and 2-5 h following regular buprenorphine dosing. A linear one-compartment POPPK model with first-order estimation was used to evaluate buprenorphine clearance (CL/F) and volume of distribution (V/F). Covariates included weight and HIV status.
All HIV+ patients reported complete past-month adherence to taking antiretroviral therapy that included either efavirenz or nevirapine. Buprenorphine CL/F was 76% higher in HIV+ patients (n = 17) than HIV- patients (n = 37). Buprenorphine V/F was 41% higher in the HIV+ patients.
POPPK can be used to model buprenorphine pharmacokinetics in a real-world clinical population. While interactions between ART and buprenorphine alter buprenorphine CL/F, we also found alteration in V/F. Proportionate changes in CL/F and V/F might indicate a primary effect on bioavailability (F) rather than two separate effects. These findings indicate reduced buprenorphine bioavailability in patients with HIV.
丁丙诺啡广泛用于治疗阿片类物质使用障碍（OUD）。针对不同人群的丁丙诺啡药代动力学模型较少。群体药代动力学（POPPK）允许在药代动力学研究中纳入协变量，从而为评估合并症、药物及其他因素对丁丙诺啡药代动力学的影响提供了可能。这项初步研究采用POPPK来探究接受丁丙诺啡治疗OUD的HIV感染者和未感染者的丁丙诺啡药代动力学。
在54例接受丁丙诺啡治疗OUD的患者中，于常规丁丙诺啡给药前及给药后2 - 5小时测定血浆丁丙诺啡水平。采用具有一级估计的线性单室POPPK模型评估丁丙诺啡清除率（CL/F）和分布容积（V/F）。协变量包括体重和HIV状态。
所有HIV阳性患者均报告在过去一个月完全坚持服用包含依非韦伦或奈韦拉平的抗逆转录病毒疗法。HIV阳性患者（n = 17）的丁丙诺啡CL/F比HIV阴性患者（n = 37）高76%。HIV阳性患者的丁丙诺啡V/F高41%。
POPPK可用于模拟真实临床人群中的丁丙诺啡药代动力学。虽然抗逆转录病毒疗法（ART）与丁丙诺啡之间的相互作用改变了丁丙诺啡CL/F，但我们也发现了V/F的改变。CL/F和V/F的成比例变化可能表明对生物利用度（F）有主要影响，而非两种独立的影响。这些发现表明HIV感染者的丁丙诺啡生物利用度降低。
