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Pharmacokinetics of Coencapsulated Antiretrovirals with Ingestible Sensors.

Abstract

We investigated the use of a system with an ingestible sensor (Proteus Digital Health Feedback system) coencapsulated with antiretrovirals (ARVs) to measure real-time adherence. To assess the safety and impact, if any, coencapsulation might have on ARV concentrations, we evaluated the pharmacokinetics of ARVs coencapsulated with an ingestible sensor for eight commonly used fixed-dose combination ARVs: emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF); FTC/tenofovir alafenamide (TAF); efavirenz (EFV)/FTC/TDF; abacavir (ABC)/lamivudine (3TC); dolutegravir (DTG)/ABC/3TC; rilpivirine (RPV)/TAF/FTC; elvitegravir (EVG)/cobicistat (COBI)/FTC/TAF; and bictegravir (BIC)/FTC/TAF. The steady-state apparent peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) were determined from plasma concentrations measured at predose, 1, 2, 4, and 6 h postdose, and compared with literature values. A total of 49 unique patients on stable regimens for at least 12 weeks with undetectable viral loads were recruited. Cmax and AUC values were not statistically significantly different from literature values for all of the formulations except the Cmax of FTC/TDF, Cmax of BIC, and the Cmax of RPV. In a subsequent evaluation of FTC/TDF and BIC/FTC/TAF using a crossover design, the geometric mean ratio (GMR) between the coencapsulated and the unencapsulated formulations for FTC/TDF were the following: FTC, 84.6% (90% confidence interval [CI] 66.6-107.4) for AUC and 77.5% (60.1-99.9) for Cmax. For tenofovir (TFV), the GMR was 96.2% (90% CI 89.2-103.8) for AUC and 87.3% (64.2-118.7) for Cmax. The GMR for BIC (from the BIC/FTC/TAF formulation) was 98.0% (90% CI 84.5-113.5) for AUC and 89.9% (84.5-95.7) for Cmax. The observed deviation in FTC/TDF (Truvada) may be due to participant characteristics, fasted/fed conditions, and/or random variation and may warrant further investigations with a larger sample size. These findings provide assurance for use of coencapsulated ARVs for future HIV treatment-adherence research.

Authors+Show Affiliations

Division of Public Health and Community Dentistry, University of California, Los Angeles (UCLA), Los Angeles, California. Department of Medicine, David Geffen School of Medicine, UCLA, Los Angeles, California. Department of Biostatistics, Fielding School of Public Health, UCLA, Los Angeles, California.Department of Medicine, Division of HIV Medicine, Lundquist Institute at Harbor-UCLA Medical Center, Torrance, California.Department of Biostatistics, Fielding School of Public Health, UCLA, Los Angeles, California. Urban Health Collaborative, Dornsife School of Public Health, Drexel University, Philadelphia, Pennsylvania.Department of Medicine, Division of HIV Medicine, Lundquist Institute at Harbor-UCLA Medical Center, Torrance, California.Center for Drug Discovery, University of Nebraska Medical Center, Omaha, Nebraska.Division of Public Health and Community Dentistry, University of California, Los Angeles (UCLA), Los Angeles, California.Department of Medicine, Division of HIV Medicine, Lundquist Institute at Harbor-UCLA Medical Center, Torrance, California.Division of Oral Biology and Medicine, School of Dentistry, UCLA, Los Angeles, California.Department of Biostatistics, Fielding School of Public Health, UCLA, Los Angeles, California.Proteus Digital Health, Redwood City, California.Proteus Digital Health, Redwood City, California.School of Medicine, Yale University, New Haven, Connecticut.Center for Drug Discovery, University of Nebraska Medical Center, Omaha, Nebraska.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31516025

Citation

Liu, Honghu, et al. "Pharmacokinetics of Coencapsulated Antiretrovirals With Ingestible Sensors." AIDS Research and Human Retroviruses, 2019.
Liu H, Daar E, Wang Y, et al. Pharmacokinetics of Coencapsulated Antiretrovirals with Ingestible Sensors. AIDS Res Hum Retroviruses. 2019.
Liu, H., Daar, E., Wang, Y., Siqueiros, L., Campbell, K., Shen, J., ... Fletcher, C. V. (2019). Pharmacokinetics of Coencapsulated Antiretrovirals with Ingestible Sensors. AIDS Research and Human Retroviruses, doi:10.1089/AID.2019.0202.
Liu H, et al. Pharmacokinetics of Coencapsulated Antiretrovirals With Ingestible Sensors. AIDS Res Hum Retroviruses. 2019 Oct 24; PubMed PMID: 31516025.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Pharmacokinetics of Coencapsulated Antiretrovirals with Ingestible Sensors. AU - Liu,Honghu, AU - Daar,Eric, AU - Wang,Yan, AU - Siqueiros,Lisa, AU - Campbell,Kayla, AU - Shen,Jie, AU - Guerrero,Mario, AU - Ko,Meng-Wei, AU - Xiong,Di, AU - Dao,John, AU - Young,Todd, AU - Rosen,Marc, AU - Fletcher,Courtney V, Y1 - 2019/10/24/ PY - 2019/9/14/pubmed PY - 2019/9/14/medline PY - 2019/9/14/entrez KW - adherence KW - antiretroviral medication KW - bioavailability KW - coencapsulated ARV KW - ingestible sensor KW - pharmacokinetics JF - AIDS research and human retroviruses JO - AIDS Res. Hum. Retroviruses N2 - We investigated the use of a system with an ingestible sensor (Proteus Digital Health Feedback system) coencapsulated with antiretrovirals (ARVs) to measure real-time adherence. To assess the safety and impact, if any, coencapsulation might have on ARV concentrations, we evaluated the pharmacokinetics of ARVs coencapsulated with an ingestible sensor for eight commonly used fixed-dose combination ARVs: emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF); FTC/tenofovir alafenamide (TAF); efavirenz (EFV)/FTC/TDF; abacavir (ABC)/lamivudine (3TC); dolutegravir (DTG)/ABC/3TC; rilpivirine (RPV)/TAF/FTC; elvitegravir (EVG)/cobicistat (COBI)/FTC/TAF; and bictegravir (BIC)/FTC/TAF. The steady-state apparent peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) were determined from plasma concentrations measured at predose, 1, 2, 4, and 6 h postdose, and compared with literature values. A total of 49 unique patients on stable regimens for at least 12 weeks with undetectable viral loads were recruited. Cmax and AUC values were not statistically significantly different from literature values for all of the formulations except the Cmax of FTC/TDF, Cmax of BIC, and the Cmax of RPV. In a subsequent evaluation of FTC/TDF and BIC/FTC/TAF using a crossover design, the geometric mean ratio (GMR) between the coencapsulated and the unencapsulated formulations for FTC/TDF were the following: FTC, 84.6% (90% confidence interval [CI] 66.6-107.4) for AUC and 77.5% (60.1-99.9) for Cmax. For tenofovir (TFV), the GMR was 96.2% (90% CI 89.2-103.8) for AUC and 87.3% (64.2-118.7) for Cmax. The GMR for BIC (from the BIC/FTC/TAF formulation) was 98.0% (90% CI 84.5-113.5) for AUC and 89.9% (84.5-95.7) for Cmax. The observed deviation in FTC/TDF (Truvada) may be due to participant characteristics, fasted/fed conditions, and/or random variation and may warrant further investigations with a larger sample size. These findings provide assurance for use of coencapsulated ARVs for future HIV treatment-adherence research. SN - 1931-8405 UR - https://www.unboundmedicine.com/medline/citation/31516025/Pharmacokinetics_of_Co-encapsulated_Antiretrovirals_with_Ingestible_Sensors L2 - https://www.liebertpub.com/doi/full/10.1089/AID.2019.0202?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -