Pharmacokinetic and Tissue Distribution Profile of Long Acting Tenofovir Alafenamide and Elvitegravir Loaded Nanoparticles in Humanized Mice Model

Pavan Kumar Prathipati, Subhra Mandal, Gregory Pon, Renuga Vivekanandan, Christopher J. Destache

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Purpose: Non-adherence to the antiretroviral (ARV) regimen is a critical factor in determining efficacy of ARV drugs for pre-exposure prophylaxis (PrEP). A long-acting parenteral formulation may be an effective alternative to daily oral dosing. A pharmacokinetic and tissue distribution study of drug-loaded nanoparticle (NP) was performed in female humanized CD34+-NSG mice. Methods: Mice received 200 mg/kg each of tenofovir alafenamide (TAF) and elvitegravir (EVG) as free drugs (TAF + EVG solution) or as drug loaded NP (TAF + EVG NP) formulation by subcutaneous (SubQ) administration. Plasma and tissue were collected to determine tenofovir (TFV) and EVG concentrations using LC-MS/MS. Non-compartmental analysis was performed using WinNonlin. Results: SubQ administration of TAF + EVG NP formulation resulted in long residence time and exposure for both drugs. The AUC(0-72h) of TFV and EVG was 14.1 ± 2.0, 7.2 ± 1.8 μg × hr./mL from drugs in solution (free) and the AUC(0-14day) for the same drugs was 23.1 ± 4.4, 39.7 ± 6.7 μg × hr./mL from NPs. The observed elimination half-life (t1/2) for TFV of free and NPs were 14.2 h, 5.1 days and for EVG 10.8 h, 3.3 days, respectively. Conclusion: This study documents that a TAF + EVG NP provides sustained release, which can overcome patient non-adherence to dosing and may facilitate prediction of appropriate protective drug concentration for HIV prophylaxis.

Original languageEnglish (US)
Pages (from-to)1-7
Number of pages7
JournalPharmaceutical Research
DOIs
StateAccepted/In press - Sep 13 2017

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Pharmacokinetics
Tissue Distribution
Nanoparticles
Tenofovir
Tissue
Pharmaceutical Preparations
Area Under Curve
Protective Agents
JTK 303
GS-7340
Patient Compliance
Half-Life
HIV
Plasmas

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry
  • Pharmacology (medical)

Cite this

Pharmacokinetic and Tissue Distribution Profile of Long Acting Tenofovir Alafenamide and Elvitegravir Loaded Nanoparticles in Humanized Mice Model. / Prathipati, Pavan Kumar; Mandal, Subhra; Pon, Gregory; Vivekanandan, Renuga; Destache, Christopher J.

In: Pharmaceutical Research, 13.09.2017, p. 1-7.

Research output: Contribution to journalArticle

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