title: Pharmacokinetics, efficacy and safety of daclatasvir plus asunaprevir in dialysis patients with chronic hepatitis C: pilot study.
abstract: The aim of this study was to evaluate the pharmacokinetic profile of daclatasvir (DCV) and asunaprevir (ASV) dual therapy in haemodialysis patients infected with hepatitis C virus (HCV). Eighteen haemodialysis patients and 54 patients with normal renal function were treated with DCV and ASV dual therapy for 24 weeks. We evaluated the pharmacokinetic profiles of DCV and ASV and examined the rate of sustained virological response 12 weeks after the end of treatment (SVR12) and incidence of adverse events during treatment of haemodialysis patients infected with chronic HCV genotype 1 infection. To adjust for potential differences in baseline characteristics between haemodialysis patients and patients with normal renal function, we used propensity scores case-control matching methods. Area under the plasma concentration time curve from 0 to 6 h (AUC0-6 h) of DCV was slightly lower in haemodialysis patients than in patients with normal renal function (P > 0.6). AUC0-6 hof ASV was significantly lower in haemodialysis patients (P = 0.012). SVR12rates were 100% (18/18) for haemodialysis and 96.2% (52/54) for patients with normal renal function. Changes in mean log10HCV RNA levels and viral response were higher in haemodialysis patients compared to patients with normal renal function. No discontinuations due to adverse events occurred. In conclusion, DCV and ASV dual therapy for HCV infection is effective and safe with similar results in haemodialysis patients compared to patients with normal renal function.
authors.affiliation: Department of Gastroenterology and Metabolism, Applied Life Sciences, Institute of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan.|Liver Research Project Center, Hiroshima University, Hiroshima, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Kawakami
authors.affiliation: Department of Gastroenterology and Metabolism, Applied Life Sciences, Institute of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan.|Liver Research Project Center, Hiroshima University, Hiroshima, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Imamura
authors.affiliation: Division of Gastroenterology and Hepatology, St. Marianna University School of Medicine, Kanagawa, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Ikeda
authors.affiliation: Division of Gastroenterology and Hepatology, St. Marianna University School of Medicine, Kanagawa, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Suzuki
authors.affiliation: Tsuchiya General Hospital, Hiroshima, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Arataki
authors.affiliation: Tsuchiya General Hospital, Hiroshima, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Moriishi
authors.affiliation: Department of Gastroenterology/Liver Center, Hiroshima Red Cross Hospital & Atomic-bomb Survivors Hospital, Hiroshima, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Mori
authors.affiliation: Department of Nephrology, Hiroshima University Hospital, Hiroshima, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Kokoroishi
authors.affiliation: Department of Gastroenterology, Onomichi General Hospital, Hiroshima, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Katamura
authors.affiliation: Department of Nephrology, Onomichi General Hospital, Hiroshima, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Ezaki
authors.affiliation: Department of Nephrology, Hiroshima University Hospital, Hiroshima, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Ueno
authors.affiliation: Department of Surgery, Division of Frontier Medical Science, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Ide
authors.affiliation: Department of Nephrology, Hiroshima University Hospital, Hiroshima, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Masaki
authors.affiliation: Department of Surgery, Division of Frontier Medical Science, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Ohdan
authors.affiliation: Department of Gastroenterology and Metabolism, Applied Life Sciences, Institute of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan. chayama@hiroshima-u.ac.jp.|Liver Research Project Center, Hiroshima University, Hiroshima, Japan. chayama@hiroshima-u.ac.jp.|Laboratory for Digestive Diseases, RIKEN Center for Integrative Medical Sciences, The Institute of Physical and Chemical Research (RIKEN), Hiroshima, Japan. chayama@hiroshima-u.ac.jp.
authors.forename: K
authors.initials: K
authors.lastname: Chayama
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000998:Antiviral Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*; D002219:Carbamates; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology; D005260:Female; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*; D015994:Incidence; D007546:Isoquinolines / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011446:Prospective Studies; D011759:Pyrrolidines; D006435:Renal Dialysis; D051437:Renal Insufficiency / Q000150:complications* / Q000628:therapy; D013449:Sulfonamides / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*; D000072230:Sustained Virologic Response; D016896:Treatment Outcome; D014633:Valine / Q000031:analogs & derivatives
chemical_list: D000998:Antiviral Agents; D002219:Carbamates; D007093:Imidazoles; D007546:Isoquinolines; D011759:Pyrrolidines; D013449:Sulfonamides; D014633:Valine; C549273:daclatasvir; C571889:asunaprevir
keywords: asunaprevir; daclatasvir; haemodialysis; pharmacokinetics