Telaprevir-S isomer enhances ribavirin exposure and the ribavirin-related haemolytic anaemia in a concentration-dependent manner
| Autor: | Antonina Smedile, Giovanni Di Perri, S. Strona, Jessica Cusato, Adnan Mohamed Abdi, Giulia Troshina, Amedeo De Nicolò, Mario Rizzetto, Alessia Ciancio, Lucio Boglione, Giuseppe Cariti, Chiara Simona Cardellino, Antonio D'Avolio, Gian Paolo Caviglia |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Adult
Male Anemia Hemolytic Renal function Context (language use) Hepacivirus Pharmacology Antiviral Agents Telaprevir chemistry.chemical_compound Isomerism Virology Boceprevir Ribavirin medicine Humans Dual therapy Dose-Response Relationship Drug medicine.diagnostic_test business.industry Interferon-alpha Hepatitis C Chronic Middle Aged Concentration dependent chemistry Therapeutic drug monitoring Drug Therapy Combination Female business Oligopeptides medicine.drug |
| Zdroj: | Antiviral Research. 109:7-14 |
| ISSN: | 0166-3542 |
| DOI: | 10.1016/j.antiviral.2014.06.005 |
| Popis: | The standard-of-care for the treatment of genotype-1 chronic hepatitis C is based on the combination of direct acting antivirals, such as boceprevir and telaprevir, with ribavirin and pegylated-interferon alfa. These triple regimens give a higher response rate than dual therapy, but on the other hand show a more than 10% higher rate of anaemia. Not enough focus has been given to the interaction between telaprevir and RBV. In this work, we aimed to study and deepen this relationship by comparing ribavirin plasma and intra-erythrocytic concentrations at one month of triple and dual therapy (17 vs. 119 patients). Moreover, we determined telaprevir isomers concentrations and tested them for correlation with ribavirin concentrations and haemoglobin loss at one month of treatment. Finally, all drugs concentration data were tested for their correlation with the renal function during treatment. The comparisons of ribavirin concentration and toxicity data were repeated on a sub-group of 9 patients who had been treated 1 year before with dual therapy and then re-treated with triple therapy. The observed ribavirin plasma and intra-erythrocytic concentrations in triple therapy were significantly higher compared to dual therapy, both in whole group and sub-group comparison. Ribavirin concentrations were significantly correlated to the haemoglobin loss and telaprevir-S isomer concentrations (r(2)=0.317 P(value)=0.023 and r(2)=0.388 P(value)=0.008, respectively). Renal function had a significant decrease from the baseline value, but was not significantly correlated with drugs concentrations. These results highlight for the first time that, in the context of triple therapy with telaprevir, ribavirin exposure is related to the telaprevir-S isomer plasma concentration. We conclude that the addition of telaprevir to the dual therapy increases ribavirin exposure and haemoglobin loss: this effect could probably be managed through the therapeutic drug monitoring of ribavirin and telaprevir-S concentrations. |
| Databáze: | OpenAIRE |
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