دورية أكاديمية
أعرض في EDS

Pharmacokinetic Study of Islatravir and Etonogestrel Implants in Macaques.

التفاصيل البيبلوغرافية
العنوان: Pharmacokinetic Study of Islatravir and Etonogestrel Implants in Macaques.
المؤلفون: Daly MB; Division of HIV/AIDS Prevention, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, GA 30329, USA., Wong-Sam A; Division of HIV/AIDS Prevention, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, GA 30329, USA., Li L; RTI International, Durham, NC 27709, USA., Krovi A; RTI International, Durham, NC 27709, USA., Gatto GJ; RTI International, Durham, NC 27709, USA., Norton C; RTI International, Durham, NC 27709, USA., Luecke EH; RTI International, Durham, NC 27709, USA., Mrotz V; Division of Scientific Resources, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30329, USA., Forero C; Division of Scientific Resources, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30329, USA., Cottrell ML; Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599, USA., Schauer AP; Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599, USA., Gary J; Division of Scientific Resources, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30329, USA., Nascimento-Seixas J; Division of Scientific Resources, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30329, USA., Mitchell J; Division of HIV/AIDS Prevention, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, GA 30329, USA., van der Straten A; ASTRA Consulting, Kensington, CA 94708, USA.; Center for AIDS Prevention Studies, Department of Medicine, University of California San Francisco, San Francisco, CA 94104, USA., Heneine W; Division of HIV/AIDS Prevention, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, GA 30329, USA., García-Lerma JG; Division of HIV/AIDS Prevention, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, GA 30329, USA., Dobard CW; Division of HIV/AIDS Prevention, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, GA 30329, USA., Johnson LM; RTI International, Durham, NC 27709, USA.
المصدر: Pharmaceutics [Pharmaceutics] 2023 Nov 26; Vol. 15 (12). Date of Electronic Publication: 2023 Nov 26.
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: The prevention of HIV and unintended pregnancies is a public health priority. Multi-purpose prevention technologies capable of long-acting HIV and pregnancy prevention are desirable for women. Here, we utilized a preclinical macaque model to evaluate the pharmacokinetics of biodegradable ε-polycaprolactone implants delivering the antiretroviral islatravir (ISL) and the contraceptive etonogestrel (ENG). Three implants were tested: ISL-62 mg, ISL-98 mg, and ENG-33 mg. Animals received one or two ISL-eluting implants, with doses of 42, 66, or 108 µg of ISL/day with or without an additional ENG-33 mg implant (31 µg/day). Drug release increased linearly with dose with median [range] plasma ISL levels of 1.3 [1.0-2.5], 1.9 [1.2-6.3] and 2.8 [2.3-11.6], respectively. The ISL-62 and 98 mg implants demonstrated stable drug release over three months with ISL-triphosphate (ISL-TP) concentr54ations in PBMCs above levels predicted to be efficacious for PrEP. Similarly, ENG implants demonstrated sustained drug release with median [range] plasma ENG levels of 495 [229-1110] pg/mL, which suppressed progesterone within two weeks and showed no evidence of altering ISL pharmacokinetics. Two of the six ISL-98 mg implants broke during the study and induced implant-site reactions, whereas no reactions were observed with intact implants. We show that ISL and ENG biodegradable implants are safe and yield sufficient drug levels to achieve prevention targets. The evaluation of optimized implants with increased mechanical robustness is underway for improved durability and vaginal efficacy in a SHIV challenge model.
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معلومات مُعتمدة: P30 AI050410 United States AI NIAID NIH HHS; P51 OD011106 United States OD NIH HHS
فهرسة مساهمة: Keywords: HIV pre-exposure prophylaxis; biodegradable implant; etonogestrel; islatravir; multipurpose prevention technologies
تواريخ الأحداث: Date Created: 20231223 Latest Revision: 20240210
رمز التحديث: 20240210
مُعرف محوري في PubMed: PMC10747562
DOI: 10.3390/pharmaceutics15122676
PMID: 38140017
قاعدة البيانات: MEDLINE
الوصف
تدمد:1999-4923
DOI:10.3390/pharmaceutics15122676