دورية أكاديمية
أعرض في EDS

Dose-Ranging Plasma and Genital Tissue Pharmacokinetics and Biodegradation of Ultra-Long-Acting Cabotegravir In Situ Forming Implant.

التفاصيل البيبلوغرافية
العنوان: Dose-Ranging Plasma and Genital Tissue Pharmacokinetics and Biodegradation of Ultra-Long-Acting Cabotegravir In Situ Forming Implant.
المؤلفون: Young IC; Division of Pharmacoengineering and Molecular Pharmaceutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA., Thorson AL; Joint Department of Biomedical Engineering, North Carolina State University and The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA., Shrivastava R; Joint Department of Biomedical Engineering, North Carolina State University and The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA., Sykes C; Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA., Schauer AP; Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA., Cottrell ML; Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA., Kashuba ADM; Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA., Benhabbour SR; Division of Pharmacoengineering and Molecular Pharmaceutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.; Joint Department of Biomedical Engineering, North Carolina State University and The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
المصدر: Pharmaceutics [Pharmaceutics] 2023 May 13; Vol. 15 (5). Date of Electronic Publication: 2023 May 13.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: MDPI Country of Publication: Switzerland NLM ID: 101534003 Publication Model: Electronic Cited Medium: Print ISSN: 1999-4923 (Print) Linking ISSN: 19994923 NLM ISO Abbreviation: Pharmaceutics Subsets: PubMed not MEDLINE
أسماء مطبوعة: Original Publication: Basel, Switzerland : MDPI
مستخلص: HIV continues to affect millions of men and women worldwide. The development of long-acting injectables for HIV prevention can overcome adherence challenges with daily oral prevention regimens by reducing dosing frequency and stigma. We previously developed an ultra-long-acting injectable, biodegradable, and removeable in situ forming implant (ISFI) with cabotegravir (CAB) that demonstrated protection after multiple rectal SHIV challenges in female macaques. Here, we sought to further characterize CAB ISFI pharmacokinetics (PK) in mice by assessing the effect of dose and number of injections on CAB PK, time to completion of CAB release and polymer degradation, long-term genital tissue PK, and CAB PK tail after implant removal. CAB concentrations in plasma were above the benchmark for protection for 11-12 months with proportionality between dose and drug exposure. CAB ISFI exhibited high concentrations in vaginal, cervical, and rectal tissues for up to 180 days. Furthermore, depots were easily retrievable up to 180 days post-administration with up to 34% residual CAB and near complete (85%) polymer degradation quantified in depots ex vivo. After depot removal, results demonstrated a median 11-fold decline in CAB plasma concentrations across all doses. Ultimately, this study provided critical PK information for the CAB ISFI formulation that could aid in its future translation to clinical studies.
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معلومات مُعتمدة: R01 AI162246 United States AI NIAID NIH HHS; KL2TR001109-04 United States TR NCATS NIH HHS
فهرسة مساهمة: Keywords: HIV; biodegradable; injectable; long acting; pharmacokinetics; polymer
تواريخ الأحداث: Date Created: 20230527 Latest Revision: 20240210
رمز التحديث: 20240210
مُعرف محوري في PubMed: PMC10222572
DOI: 10.3390/pharmaceutics15051487
PMID: 37242729
قاعدة البيانات: MEDLINE
الوصف
تدمد:1999-4923
DOI:10.3390/pharmaceutics15051487