Abstract
Background: 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. Methods: 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. Results: 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. Conclusions: 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.
Original language | English (US) |
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Article number | 109696 |
Journal | Drug and alcohol dependence |
Volume | 241 |
DOIs | |
State | Published - Dec 1 2022 |
Bibliographical note
Funding Information:The authors would like to acknowledge Dr. Jag Khalsa for early support of the grant, Drs. Tam Nguyen Thi Minh and Thanh Van Ta for supporting implementation of this study in Vietnam, Mr. James Fisher for establishing and conducting the buprenorphine assays, Project Management support of Hoang Yen, Nate Tessum, and Lynn Kunkel, the research assistant support of Ms. Carnayla Johnson, and the HMU CREATA team.
Funding Information:
Research reported in this publication was supported by the National Institute on Drug Abuse of the National Institutes of Health under Award Number R01DA040510 (GB) and R01DA037441 (PTK). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Publisher Copyright:
© 2022 Elsevier B.V.
Keywords
- Buprenorphine
- HIV
- Opioid use disorder
- Pharmacokinetics
- Vietnam