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 language | English (US) |
|---|---|
| Pages (from-to) | 1-7 |
| Number of pages | 7 |
| Journal | Pharmaceutical Research |
| DOIs | |
| State | Accepted/In press - Sep 13 2017 |
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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 journal › Article
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TY - JOUR
T1 - Pharmacokinetic and Tissue Distribution Profile of Long Acting Tenofovir Alafenamide and Elvitegravir Loaded Nanoparticles in Humanized Mice Model
AU - Prathipati, Pavan Kumar
AU - Mandal, Subhra
AU - Pon, Gregory
AU - Vivekanandan, Renuga
AU - Destache, Christopher J.
PY - 2017/9/13
Y1 - 2017/9/13
N2 - 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.
AB - 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.
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U2 - 10.1007/s11095-017-2255-7
DO - 10.1007/s11095-017-2255-7
M3 - Article
C2 - 28905173
AN - SCOPUS:85029441293
SP - 1
EP - 7
JO - Pharmaceutical Research
JF - Pharmaceutical Research
SN - 0724-8741
ER -