Assessment of Pharmacokinetic Interaction Between Letermovir and Fluconazole in Healthy Participants
© 2020, The American College of Clinical Pharmacology..
Letermovir is a prophylactic agent for cytomegalovirus infection and disease in adult cytomegalovirus-seropositive recipients of allogeneic hematopoietic stem cell transplant. As the antifungal agent fluconazole is administered frequently in transplant recipients, a drug-drug interaction study was conducted between oral letermovir and oral fluconazole. A phase 1 open-label, fixed-sequence study was performed in healthy females (N = 14, 19-55 years). In Period 1, a single dose of fluconazole 400 mg was administered. Following a 14-day washout, a single dose of letermovir 480 mg was administered (Period 2), and after a 7-day washout, single doses of fluconazole 400 mg and letermovir 480 mg were coadministered in Period 3. Pharmacokinetics and safety were evaluated. The pharmacokinetics of fluconazole and letermovir were not meaningfully changed following coadministration. Fluconazole geometric mean ratio (GMR; 90% confidence interval [CI]) with letermovir for area under the concentration-versus-time curve from time 0 to infinity (AUC0-∞ ) was 1.03 (0.99-1.08); maximum concentration (Cmax ) was 0.95 (0.92-0.99). Letermovir AUC0-∞ GMR (90%CI) was 1.11 (1.01-1.23), and Cmax was 1.06 (0.93-1.21) following coadministration with fluconazole. Coadministration of fluconazole and letermovir was generally well tolerated.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:10 |
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| Enthalten in: |
Clinical pharmacology in drug development - 10(2021), 2 vom: 02. Feb., Seite 198-206 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Adedoyin, Adedayo [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 14.12.2021 Date Revised 14.12.2021 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1002/cpdd.852 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM312765681 |
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| 245 | 1 | 0 | |a Assessment of Pharmacokinetic Interaction Between Letermovir and Fluconazole in Healthy Participants |
| 264 | 1 | |c 2021 | |
| 336 | |a Text |b txt |2 rdacontent | ||
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| 500 | |a Date Completed 14.12.2021 | ||
| 500 | |a Date Revised 14.12.2021 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2020, The American College of Clinical Pharmacology. | ||
| 520 | |a Letermovir is a prophylactic agent for cytomegalovirus infection and disease in adult cytomegalovirus-seropositive recipients of allogeneic hematopoietic stem cell transplant. As the antifungal agent fluconazole is administered frequently in transplant recipients, a drug-drug interaction study was conducted between oral letermovir and oral fluconazole. A phase 1 open-label, fixed-sequence study was performed in healthy females (N = 14, 19-55 years). In Period 1, a single dose of fluconazole 400 mg was administered. Following a 14-day washout, a single dose of letermovir 480 mg was administered (Period 2), and after a 7-day washout, single doses of fluconazole 400 mg and letermovir 480 mg were coadministered in Period 3. Pharmacokinetics and safety were evaluated. The pharmacokinetics of fluconazole and letermovir were not meaningfully changed following coadministration. Fluconazole geometric mean ratio (GMR; 90% confidence interval [CI]) with letermovir for area under the concentration-versus-time curve from time 0 to infinity (AUC0-∞ ) was 1.03 (0.99-1.08); maximum concentration (Cmax ) was 0.95 (0.92-0.99). Letermovir AUC0-∞ GMR (90%CI) was 1.11 (1.01-1.23), and Cmax was 1.06 (0.93-1.21) following coadministration with fluconazole. Coadministration of fluconazole and letermovir was generally well tolerated | ||
| 650 | 4 | |a Clinical Trial, Phase I | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a allogeneic hematopoietic stem cell transplant recipients | |
| 650 | 4 | |a cytomegalovirus | |
| 650 | 4 | |a drug-drug interaction | |
| 650 | 4 | |a fluconazole | |
| 650 | 4 | |a letermovir | |
| 650 | 4 | |a pharmacokinetics | |
| 650 | 7 | |a Acetates |2 NLM | |
| 650 | 7 | |a Antifungal Agents |2 NLM | |
| 650 | 7 | |a Antiviral Agents |2 NLM | |
| 650 | 7 | |a Quinazolines |2 NLM | |
| 650 | 7 | |a letermovir |2 NLM | |
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| 650 | 7 | |a Fluconazole |2 NLM | |
| 650 | 7 | |a 8VZV102JFY |2 NLM | |
| 700 | 1 | |a Fancourt, Craig |e verfasserin |4 aut | |
| 700 | 1 | |a Menzel, Karsten |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Tian |e verfasserin |4 aut | |
| 700 | 1 | |a Tomek, Charles |e verfasserin |4 aut | |
| 700 | 1 | |a Panebianco, Deborah |e verfasserin |4 aut | |
| 700 | 1 | |a McCrea, Jacqueline B |e verfasserin |4 aut | |
| 700 | 1 | |a Stoch, S Aubrey |e verfasserin |4 aut | |
| 700 | 1 | |a Iwamoto, Marian |e verfasserin |4 aut | |
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