Assessment of Drug Interaction Potential Between the Hepatitis C Virus Direct‐Acting Antiviral Agents Elbasvir/Grazoprevir and the Nucleotide Analog Reverse‐Transcriptase Inhibitor Tenofovir Disoproxil Fumarate
| العنوان: | Assessment of Drug Interaction Potential Between the Hepatitis C Virus Direct‐Acting Antiviral Agents Elbasvir/Grazoprevir and the Nucleotide Analog Reverse‐Transcriptase Inhibitor Tenofovir Disoproxil Fumarate |
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| المؤلفون: | William D. Hanley, Yali Zhu, William L. Marshall, Luzelena Caro, Hwa-Ping Feng, Eric Mangin, Deborah Panebianco, Xiaobi Huang, Robert Valesky, Jennifer Talaty, Monika Martinho, Joan R. Butterton, Patricia Jumes, Christine Fandozzi, Zifang Guo, Wendy W. Yeh, Marian Iwamoto |
| المصدر: | Clinical Pharmacology in Drug Development. 8:962-970 |
| بيانات النشر: | Wiley, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Adult, Male, Elbasvir, Hepatitis C virus, Pharmaceutical Science, Hepacivirus, Pharmacology, medicine.disease_cause, Antiviral Agents, 030226 pharmacology & pharmacy, Drug Administration Schedule, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Pharmacokinetics, Quinoxalines, medicine, Humans, Elbasvir, Grazoprevir, Drug Interactions, Pharmacology (medical), Tenofovir, Benzofurans, Reverse-transcriptase inhibitor, business.industry, Imidazoles, HIV, Hepatitis C, Middle Aged, Drug interaction, medicine.disease, Healthy Volunteers, Drug Combinations, Grazoprevir, Area Under Curve, 030220 oncology & carcinogenesis, Reverse Transcriptase Inhibitors, Female, business, medicine.drug |
| الوصف: | Treatment of individuals coinfected with hepatitis C virus (HCV) and human immunodeficiency virus (HIV) requires careful consideration of potential drug-drug interactions. We evaluated the pharmacokinetic interaction of the direct-acting antiviral agents elbasvir and grazoprevir coadministered with the nucleotide reverse transcriptase inhibitor tenofovir disoproxil fumarate (TDF). Three open-label, multidose studies in healthy adults were conducted. In the first study (N = 10), participants received TDF 300 mg once daily, elbasvir 50 mg once daily, and elbasvir coadministered with TDF. In the second study (N = 12), participants received TDF 300 mg once daily, grazoprevir 200 mg once daily, and grazoprevir coadministered with TDF. In the third study (N = 14), participants received TDF 300 mg once daily and TDF 300 mg coadministered with coformulated elbasvir/grazoprevir 50 mg/100 mg once daily. Pharmacokinetics and safety were evaluated. Following coadministration, the tenofovir area under the plasma concentration-time curve to 24 hours and maximum plasma concentration geometric mean ratios (90% confidence intervals) for tenofovir and coadministered drug(s) versus tenofovir were 1.3 (1.2, 1.5) and 1.5 (1.3, 1.6), respectively, when coadministered with elbasvir; 1.2 (1.1, 1.3) and 1.1 (1.0, 1.2), respectively, when coadministered with grazoprevir; and 1.3 (1.2, 1.4) and 1.1 (1.0, 1.4), respectively, when coadministered with the elbasvir/grazoprevir coformulation. TDF had minimal effect on elbasvir and grazoprevir pharmacokinetics. Elbasvir and/or grazoprevir coadministered with TDF resulted in no clinically meaningful tenofovir exposure increases and was generally well tolerated, with no deaths, serious adverse events (AEs), discontinuations due to AEs, or laboratory AEs reported. No dose adjustments for elbasvir/grazoprevir or TDF are needed for coadministration in HCV/HIV-coinfected people. |
| تدمد: | 2160-7648 2160-763X |
| DOI: | 10.1002/cpdd.701 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a9a42966b426c387ac34b77c65f59795 https://doi.org/10.1002/cpdd.701 |
| Rights: | CLOSED |
| رقم الانضمام: | edsair.doi.dedup.....a9a42966b426c387ac34b77c65f59795 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 21607648 2160763X |
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| DOI: | 10.1002/cpdd.701 |