Extended cell and plasma drug levels after one dose of a three-in-one nanosuspension containing lopinavir, efavirenz, and tenofovir in nonhuman primates
OBJECTIVE: To characterize a drug-combination nanoparticle (DcNP) containing water-insoluble lopinavir (LPV) and efavirenz (EFV), and water-soluble tenofovir (TFV), for its potential as a long-acting combination HIV treatment.
DESIGN: Three HIV drugs (LPV, EFV, TFV) with well established efficacy and safety were coformulated into a single DcNP suspension. Two macaques were administered one subcutaneous injection and drug concentrations in plasma and mononuclear cells (in peripheral blood and lymph nodes) were analyzed over 2 weeks. Pharmacokinetic parameters and cell-to-plasma relationships of LPV, EFV, and TFV were determined.
RESULTS: This three-in-one nanoformulation provided extended concentrations of all drugs in lymph node cells that were 57- to 228-fold higher than those in plasma. Levels of all three drugs in peripheral blood mononuclear cells persisted for 2 weeks at levels equal to or higher than those in plasma.
CONCLUSION: With long-acting characteristics and higher drug penetration/persistence in cells, this three-in-one DcNP may enhance therapeutic efficacy of these well studied HIV drugs due to colocalization and targeting of this three-drug combination to HIV host cells.
| Errataetall: |
CommentIn: AIDS. 2018 Nov 13;32(17):2625-2627. - PMID 30379688 |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2018 |
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| Erschienen: |
2018 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:32 |
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| Enthalten in: |
AIDS (London, England) - 32(2018), 17 vom: 13. Nov., Seite 2463-2467 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Koehn, Josefin [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 30.10.2019 Date Revised 09.12.2020 published: Print CommentIn: AIDS. 2018 Nov 13;32(17):2625-2627. - PMID 30379688 Citation Status MEDLINE |
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| doi: |
10.1097/QAD.0000000000001969 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM287416232 |
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| 100 | 1 | |a Koehn, Josefin |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Extended cell and plasma drug levels after one dose of a three-in-one nanosuspension containing lopinavir, efavirenz, and tenofovir in nonhuman primates |
| 264 | 1 | |c 2018 | |
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| 500 | |a Date Completed 30.10.2019 | ||
| 500 | |a Date Revised 09.12.2020 | ||
| 500 | |a published: Print | ||
| 500 | |a CommentIn: AIDS. 2018 Nov 13;32(17):2625-2627. - PMID 30379688 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a OBJECTIVE: To characterize a drug-combination nanoparticle (DcNP) containing water-insoluble lopinavir (LPV) and efavirenz (EFV), and water-soluble tenofovir (TFV), for its potential as a long-acting combination HIV treatment | ||
| 520 | |a DESIGN: Three HIV drugs (LPV, EFV, TFV) with well established efficacy and safety were coformulated into a single DcNP suspension. Two macaques were administered one subcutaneous injection and drug concentrations in plasma and mononuclear cells (in peripheral blood and lymph nodes) were analyzed over 2 weeks. Pharmacokinetic parameters and cell-to-plasma relationships of LPV, EFV, and TFV were determined | ||
| 520 | |a RESULTS: This three-in-one nanoformulation provided extended concentrations of all drugs in lymph node cells that were 57- to 228-fold higher than those in plasma. Levels of all three drugs in peripheral blood mononuclear cells persisted for 2 weeks at levels equal to or higher than those in plasma | ||
| 520 | |a CONCLUSION: With long-acting characteristics and higher drug penetration/persistence in cells, this three-in-one DcNP may enhance therapeutic efficacy of these well studied HIV drugs due to colocalization and targeting of this three-drug combination to HIV host cells | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 7 | |a Alkynes |2 NLM | |
| 650 | 7 | |a Anti-HIV Agents |2 NLM | |
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| 650 | 7 | |a Benzoxazines |2 NLM | |
| 650 | 7 | |a Cyclopropanes |2 NLM | |
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| 700 | 1 | |a Collier, Ann C |e verfasserin |4 aut | |
| 700 | 1 | |a Ho, Rodney J Y |e verfasserin |4 aut | |
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