title: Pharmacokinetics and Tolerability of Anti-Hepatitis C Virus Treatment with Ombitasvir, Paritaprevir, Ritonavir, with or Without Dasabuvir, in Subjects with Renal Impairment.
abstract: The direct-acting antiviral agent (DAA) combination of ombitasvir and paritaprevir (administered with ritonavir) with (3D regimen) or without (2D regimen) dasabuvir has shown very high efficacy rates in the treatment of chronic hepatitis C virus (HCV) infection. Renal impairment, a common comorbidity in patients with chronic HCV infection, can influence the pharmacokinetics of antiviral agents and hence their efficacy and safety profiles.
  
  
  
  The aim of this study was to evaluate the influence of renal impairment on the pharmacokinetics and tolerability of the 3D and 2D regimens.
  
  
  
  Overall, 24 subjects, six in each of four renal function groups (normal, mild, moderate, and severe), received a single dose of the 3D and 2D regimens in separate dosing periods. Plasma and urine were analyzed to assess the effect of renal impairment on drug exposure.
  
  
  
  DAA exposures changed by up to 21, 37, and 50 % in subjects with mild, moderate, and severe renal impairment, respectively, versus subjects with normal renal function. Ritonavir exposure increased with the degree of renal impairment (maximum 114 %). The half-lives of DAAs and ritonavir in subjects with renal impairment were generally comparable with those in healthy subjects. No safety or tolerability concerns arose in this study.
  
  
  
  The 3D and 2D regimens do not require dose adjustment for patients with HCV infection and concomitant renal impairment.
authors.affiliation: Clinical Pharmacology and Pharmacometrics, AbbVie Inc., Dept. R4PK, Bldg. AP-31-3, 1 North Waukegan Rd, North Chicago, IL, 60064, USA. amit.khatri@abbvie.com.
authors.forename: Amit
authors.initials: A
authors.lastname: Khatri
authors.affiliation: Clinical Pharmacology and Pharmacometrics, AbbVie Inc., Dept. R4PK, Bldg. AP-31-3, 1 North Waukegan Rd, North Chicago, IL, 60064, USA.
authors.forename: Sandeep
authors.initials: S
authors.lastname: Dutta
authors.affiliation: Clinical Research, Orlando Clinical Research Center, Orlando, FL, USA.
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Marbury
authors.affiliation: Division of Clinical Pharmacology, Department of Medicine, Miller School of Medicine, University of Miami, Miami, FL, USA.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Preston
authors.affiliation: Antiviral Global Project Team, AbbVie Inc., North Chicago, IL, USA.
authors.forename: Lino
authors.initials: L
authors.lastname: Rodrigues
authors.affiliation: Biometrics, AbbVie Inc., North Chicago, IL, USA.
authors.forename: Haoyu
authors.initials: H
authors.lastname: Wang
authors.affiliation: Clinical Pharmacology and Pharmacometrics, AbbVie Inc., Dept. R4PK, Bldg. AP-31-3, 1 North Waukegan Rd, North Chicago, IL, 60064, USA.
authors.forename: Walid M
authors.initials: WM
authors.lastname: Awni
authors.affiliation: Clinical Pharmacology and Pharmacometrics, AbbVie Inc., Dept. R4PK, Bldg. AP-31-3, 1 North Waukegan Rd, North Chicago, IL, 60064, USA.
authors.forename: Rajeev M
authors.initials: RM
authors.lastname: Menon
mesh_terms: D015081:2-Naphthylamine; D000368:Aged; D000813:Anilides / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D000998:Antiviral Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D002219:Carbamates / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D003521:Cyclopropanes; D004359:Drug Therapy, Combination; D005260:Female; D016174:Hepacivirus / Q000187:drug effects / Q000378:metabolism; D019698:Hepatitis C, Chronic / Q000097:blood* / Q000188:drug therapy / Q000453:epidemiology; D006801:Humans; D007674:Kidney Diseases / Q000097:blood* / Q000188:drug therapy / Q000453:epidemiology; D047029:Lactams, Macrocyclic; D047028:Macrocyclic Compounds / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D011392:Proline / Q000031:analogs & derivatives; D019438:Ritonavir / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D013449:Sulfonamides / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D016896:Treatment Outcome; D014498:Uracil / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D014633:Valine
chemical_list: D000813:Anilides; D000998:Antiviral Agents; D002219:Carbamates; D003521:Cyclopropanes; D047029:Lactams, Macrocyclic; D047028:Macrocyclic Compounds; D013449:Sulfonamides; C586094:ombitasvir; D014498:Uracil; D011392:Proline; D015081:2-Naphthylamine; C588260:dasabuvir; D014633:Valine; D019438:Ritonavir; C585405:paritaprevir