Pharmacokinetics, Safety, and Tolerability of Ravidasvir, with and without Danoprevir/Ritonavir, in Healthy Subjects
Ravidasvir (RDV) is a novel oral hepatitis C virus NS5A inhibitor. This study aimed to evaluate the pharmacokinetics and safety of RDV and the drug-drug interactions between RDV and ritonavir-boosted danoprevir (DNVr) in healthy adults. In the 1st study, healthy volunteers were administered single oral doses of 100, 200, and 300 mg of RDV and 200 mg once daily for 7 days. The 2nd study was a randomized, double-blinded, and placebo-controlled sequential design (day 1 for 200 mg of RDV alone, day 7 for 100 mg/100 mg of DNVr, day 13 for 200 mg of RDV plus 100 mg/100 mg DNVr, followed by 200 mg of RDV once daily with 100 mg/100 mg of DNVr twice daily for 10 days). The results showed that RDV exposure increased in a dose-proportional manner following a single dose with no evidence of accumulation with multiple doses. Coadministration with DNVr (100 mg/100 mg, twice daily) resulted in a 2.92-fold and 1.99-fold increase in minimum plasma concentration at steady state (Cmin,ss) and area under the concentration-time curve at steady state (AUCτ) of RDV, respectively. With coadministration of RDV, maximum plasma concentration (Cmax) and area under the concentration-time curve from 0 to 12 h (AUC0-12) of DNV increased 1.71-fold and 2.33-fold, respectively. We did not observe any significant changes in ritonavir exposure. Both single and multiple doses of RDV with or without DNVr were well tolerated. The favorable pharmacokinetic and safety results support ravidasvir's continued clinical development and treatment. (The studies described in this paper have been registered at ClinicalTrials.gov under identifiers NCT03430830 and NCT03288636.).
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:65 |
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| Enthalten in: |
Antimicrobial agents and chemotherapy - 65(2021), 10 vom: 17. Sept., Seite e0060021 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Wu, Guolan [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 22.09.2021 Date Revised 18.03.2022 published: Print-Electronic ClinicalTrials.gov: NCT03288636, NCT03430830 Citation Status MEDLINE |
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| doi: |
10.1128/AAC.00600-21 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM32798077X |
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| 100 | 1 | |a Wu, Guolan |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Pharmacokinetics, Safety, and Tolerability of Ravidasvir, with and without Danoprevir/Ritonavir, in Healthy Subjects |
| 264 | 1 | |c 2021 | |
| 336 | |a Text |b txt |2 rdacontent | ||
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| 500 | |a Date Completed 22.09.2021 | ||
| 500 | |a Date Revised 18.03.2022 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a ClinicalTrials.gov: NCT03288636, NCT03430830 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Ravidasvir (RDV) is a novel oral hepatitis C virus NS5A inhibitor. This study aimed to evaluate the pharmacokinetics and safety of RDV and the drug-drug interactions between RDV and ritonavir-boosted danoprevir (DNVr) in healthy adults. In the 1st study, healthy volunteers were administered single oral doses of 100, 200, and 300 mg of RDV and 200 mg once daily for 7 days. The 2nd study was a randomized, double-blinded, and placebo-controlled sequential design (day 1 for 200 mg of RDV alone, day 7 for 100 mg/100 mg of DNVr, day 13 for 200 mg of RDV plus 100 mg/100 mg DNVr, followed by 200 mg of RDV once daily with 100 mg/100 mg of DNVr twice daily for 10 days). The results showed that RDV exposure increased in a dose-proportional manner following a single dose with no evidence of accumulation with multiple doses. Coadministration with DNVr (100 mg/100 mg, twice daily) resulted in a 2.92-fold and 1.99-fold increase in minimum plasma concentration at steady state (Cmin,ss) and area under the concentration-time curve at steady state (AUCτ) of RDV, respectively. With coadministration of RDV, maximum plasma concentration (Cmax) and area under the concentration-time curve from 0 to 12 h (AUC0-12) of DNV increased 1.71-fold and 2.33-fold, respectively. We did not observe any significant changes in ritonavir exposure. Both single and multiple doses of RDV with or without DNVr were well tolerated. The favorable pharmacokinetic and safety results support ravidasvir's continued clinical development and treatment. (The studies described in this paper have been registered at ClinicalTrials.gov under identifiers NCT03430830 and NCT03288636.) | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Randomized Controlled Trial | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a drug-drug interactions | |
| 650 | 4 | |a hepatitis C | |
| 650 | 4 | |a pharmacokinetics | |
| 650 | 4 | |a ravidasvir | |
| 650 | 4 | |a safety | |
| 650 | 7 | |a Benzimidazoles |2 NLM | |
| 650 | 7 | |a Cyclopropanes |2 NLM | |
| 650 | 7 | |a Isoindoles |2 NLM | |
| 650 | 7 | |a Lactams |2 NLM | |
| 650 | 7 | |a Lactams, Macrocyclic |2 NLM | |
| 650 | 7 | |a Sulfonamides |2 NLM | |
| 650 | 7 | |a ravidasvir |2 NLM | |
| 650 | 7 | |a danoprevir |2 NLM | |
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| 650 | 7 | |a Ritonavir |2 NLM | |
| 650 | 7 | |a O3J8G9O825 |2 NLM | |
| 700 | 1 | |a Zhou, Huili |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Jing |e verfasserin |4 aut | |
| 700 | 1 | |a Lv, Duo |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Lihua |e verfasserin |4 aut | |
| 700 | 1 | |a Zhai, You |e verfasserin |4 aut | |
| 700 | 1 | |a Lin, Meihua |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Jingzi J |e verfasserin |4 aut | |
| 700 | 1 | |a Shentu, Jianzhong |e verfasserin |4 aut | |
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