Fine‐Needle Aspiration for the Evaluation of Hepatic Pharmacokinetics of Vaniprevir: A Randomized Trial in Patients With Hepatitis C Virus Infection
| Autor: | Iain P. Fraser, Larissa Wenning, Eric Mangin, Bonnie J. Howell, Christine Fandozzi, Jill Maxwell, W. Gao, Radha Railkar, Kristien Van Dyck, Chris Chung, Norah J. Shire, Andrew H. Talal, Melanie Anderson, Luzelena Caro, Serghei Popa, Andrea L. Webber, André M. M. Miltenburg, S. Aubrey Stoch |
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| Rok vydání: | 2020 |
| Předmět: |
Adult
Cyclopropanes Male medicine.medical_specialty Genotype Proline Lactams Macrocyclic Vaniprevir Hepatitis C virus Biopsy Fine-Needle Hepacivirus Isoindoles medicine.disease_cause Antiviral Agents 030226 pharmacology & pharmacy Gastroenterology Young Adult 03 medical and health sciences Liver disease chemistry.chemical_compound 0302 clinical medicine Pharmacokinetics Leucine Internal medicine Biopsy medicine Humans Tissue Distribution Pharmacology (medical) Sampling (medicine) Pharmacology Sulfonamides medicine.diagnostic_test business.industry Hepatitis C Hepatitis C Chronic Middle Aged medicine.disease body regions Fine-needle aspiration Liver chemistry 030220 oncology & carcinogenesis Female business |
| Zdroj: | Clinical Pharmacology & Therapeutics. 107:1325-1333 |
| ISSN: | 1532-6535 0009-9236 |
| DOI: | 10.1002/cpt.1737 |
| Popis: | Fine-needle aspiration (FNA) for serial hepatic sampling may be an efficient and less invasive alternative to core needle biopsy (CNB), the current standard for liver tissue sampling. In this randomized, open-label trial in 31 participants with hepatitis C virus genotype 1 infection (NCT01678131/Merck protocol PN048), we evaluated the feasibility of using FNA to obtain human liver tissue samples appropriate for measuring hepatic pharmacokinetics (PK), using vaniprevir as a tool compound. The primary end point was successful retrieval of liver tissue specimens with measurable vaniprevir concentrations at two of three specified FNA time points. Twenty-nine patients met the primary end point and, therefore, were included in the PK analyses. Hepatic vaniprevir concentrations obtained with FNA were consistent with known vaniprevir PK properties. The shape of liver FNA and CNB concentration-time profiles were comparable. In conclusion, FNA may be effective for serial tissue sampling to assess hepatic drug exposure in patients with liver disease. |
| Databáze: | OpenAIRE |
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