Pharmacological Validation of Long-Term Treatment with Antiretroviral Drugs in a Model of SIV-Infected Non-Human Primates
Abstract
:1. Introduction
2. Materials and Methods
2.1. Animals
2.2. Antiretroviral Drug Formulations
2.3. Single-Dose Antiretroviral Drug Plasma Pharmacokinetic Study
2.4. Repeated Antiretroviral Doses in Long-Term ART-Treated SIV-Infected NHP
2.5. Blood Samples and Antiretroviral Drug Assays
2.6. Efficacy and Safety Assessments
2.7. Pharmacokinetic Analysis
2.8. Statistical Analysis
3. Results
3.1. Single-Dose Antiretroviral Drug Plasma Pharmacokinetic Study
3.2. Pharmacokinetics, Efficacy, and Safety in the Long-Term Treatment Model
4. Discussion
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Cmax (ng/mL) | Tmax (h) | C24h (ng/mL) | t½ (h) | AUC0→24h (ng·h/mL) | |
---|---|---|---|---|---|
Tenofovir | |||||
PO (n = 2) | 1668 231 | 1.0 6.0 | 272 88 | 31.0 14.2 | 11,115 3857 |
SC (n = 7) | 1103 (954–1654) | 1.0 (1.0–2.0) | 32 (16–50) | 4.7 (1.2–6.1) | 4391 (2326–8598) |
IV (n = 4) | 2096 (1583–2352) | 0.25 (0.25–0.25) | 21 (12–38) | 5.1 (1.4–14.1) | 1983 (1825–2570) |
Emtricitabine | |||||
PO (n = 2) | 5062 2957 | 1.0 4.0 | 632 87 | 9.6 4.8 | 42,768 19,280 |
SC (n = 7) | 25,882 (19,607–28,634) | 1.0 (1.0–1.0) | 44 (29–61) | 3.1 (2.6–3.2) | 79,578 (76,106–96,001) |
IV (n = 4) | 67,732 (62,920–70,569) | 0.25 (0.25–0.25) | 58 (54–127) | 3.0 (2.8–3.2) | 111,530 (106,512–116,484) |
Dolutegravir | |||||
PO (n = 2) | 5105 2550 | 6.0 4.0 | 1109 113 | 8.2 4.1 | 72,426 23,956 |
SC (n = 7) | 1229 (1082–1467) | 1.0 (1.0–2.0) | 224 (180–281) | 9.2 (8.8–9.7) | 15,352 (11,401–16,540) |
IV (n = 4) | 11,643 (10,995–12,583) | 0.25 (0.25–0.25) | 86 (82–102) | 3.8 (3.7–4.2) | 39,601 (37,865–42,241) |
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Gelé, T.; Gouget, H.; Dereuddre-Bosquet, N.; Furlan, V.; Le Grand, R.; Lambotte, O.; Desjardins, D.; Barrail-Tran, A. Pharmacological Validation of Long-Term Treatment with Antiretroviral Drugs in a Model of SIV-Infected Non-Human Primates. Pharmaceutics 2022, 14, 2282. https://doi.org/10.3390/pharmaceutics14112282
Gelé T, Gouget H, Dereuddre-Bosquet N, Furlan V, Le Grand R, Lambotte O, Desjardins D, Barrail-Tran A. Pharmacological Validation of Long-Term Treatment with Antiretroviral Drugs in a Model of SIV-Infected Non-Human Primates. Pharmaceutics. 2022; 14(11):2282. https://doi.org/10.3390/pharmaceutics14112282
Chicago/Turabian StyleGelé, Thibaut, Hélène Gouget, Nathalie Dereuddre-Bosquet, Valérie Furlan, Roger Le Grand, Olivier Lambotte, Delphine Desjardins, and Aurélie Barrail-Tran. 2022. "Pharmacological Validation of Long-Term Treatment with Antiretroviral Drugs in a Model of SIV-Infected Non-Human Primates" Pharmaceutics 14, no. 11: 2282. https://doi.org/10.3390/pharmaceutics14112282
APA StyleGelé, T., Gouget, H., Dereuddre-Bosquet, N., Furlan, V., Le Grand, R., Lambotte, O., Desjardins, D., & Barrail-Tran, A. (2022). Pharmacological Validation of Long-Term Treatment with Antiretroviral Drugs in a Model of SIV-Infected Non-Human Primates. Pharmaceutics, 14(11), 2282. https://doi.org/10.3390/pharmaceutics14112282