PMID- 24080649
OWN - NLM
STAT- MEDLINE
DCOM- 20141222
LR  - 20220330
IS  - 1098-6596 (Electronic)
IS  - 0066-4804 (Print)
IS  - 0066-4804 (Linking)
VI  - 57
IP  - 12
DP  - 2013 Dec
TI  - Safety, tolerability, and pharmacokinetics of ribavirin in hepatitis C 
      virus-infected patients with various degrees of renal impairment.
PG  - 6097-105
LID - 10.1128/AAC.00608-13 [doi]
AB  - Ribavirin (RBV) is an integral part of standard-of-care hepatitis C virus (HCV) 
      treatments and many future regimens under investigation. The pharmacokinetics 
      (PK), safety, and tolerability of RBV in chronically HCV-infected patients with 
      renal impairment are not well defined and were the focus of an open-label PK 
      study in HCV-infected patients receiving RBV plus pegylated interferon. Serial 
      RBV plasma samples were collected over 12 h on day 1 of weeks 1 and 12 from 
      patients with moderate renal impairment (creatinine clearance [CLCR], 30 to 50 
      ml/min; RBV, 600 mg daily), severe renal impairment (CLCR, <30 ml/min; RBV, 400 
      mg daily), end-stage renal disease (ESRD) (RBV, 200 mg daily), or normal renal 
      function (CLCR, >80 ml/min; RBV, 800 to 1,200 mg daily). Of the 44 patients, 9 
      had moderately impaired renal function, 10 had severely impaired renal function, 
      13 had ESRD, and 12 had normal renal function. The RBV dose was reduced because 
      of adverse events (AEs) in 71% and 53% of severe and moderate renal impairment 
      groups, respectively. Despite this modification, patients with moderate and 
      severe impairment had 12-hour (area under the concentration-time curve from 0 to 
      12 h [AUC0-12]) values 36% (38,452 ng . h/ml) and 25% (35,101 ng . h/ml) higher, 
      respectively, than those with normal renal function (28,192 ng . h/ml). Patients 
      with ESRD tolerated a 200-mg daily dose, and AUC0-12 was 20% lower (22,629 ng . 
      h/ml) than in patients with normal renal function. PK modeling and simulation 
      (M&S) indicated that doses of 200 mg or 400 mg alternating daily for patients 
      with moderate renal impairment and 200 mg daily for patients with severe renal 
      impairment were the most appropriate dose regimens in these patients.
FAU - Brennan, B J
AU  - Brennan BJ
AD  - Hoffmann-La Roche, Nutley, New Jersey, USA.
FAU - Wang, K
AU  - Wang K
FAU - Blotner, S
AU  - Blotner S
FAU - Magnusson, M O
AU  - Magnusson MO
FAU - Wilkins, J J
AU  - Wilkins JJ
FAU - Martin, P
AU  - Martin P
FAU - Solsky, J
AU  - Solsky J
FAU - Nieforth, K
AU  - Nieforth K
FAU - Wat, C
AU  - Wat C
FAU - Grippo, J F
AU  - Grippo JF
LA  - eng
PT  - Clinical Trial
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20130930
PL  - United States
TA  - Antimicrob Agents Chemother
JT  - Antimicrobial agents and chemotherapy
JID - 0315061
RN  - 0 (Antiviral Agents)
RN  - 0 (Interferon-alpha)
RN  - 0 (Recombinant Proteins)
RN  - 3WJQ0SDW1A (Polyethylene Glycols)
RN  - 49717AWG6K (Ribavirin)
RN  - Q46947FE7K (peginterferon alfa-2a)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Antiviral Agents/blood/*pharmacokinetics/pharmacology
MH  - Area Under Curve
MH  - Drug Administration Schedule
MH  - Drug Dosage Calculations
MH  - Female
MH  - Hepacivirus/drug effects/physiology
MH  - Hepatitis C, Chronic/blood/complications/*drug therapy/virology
MH  - Humans
MH  - Interferon-alpha/blood/*pharmacokinetics/pharmacology
MH  - Male
MH  - Metabolic Clearance Rate
MH  - Middle Aged
MH  - Polyethylene Glycols/*pharmacokinetics/pharmacology
MH  - Recombinant Proteins/blood/pharmacokinetics/pharmacology
MH  - Renal Insufficiency/blood/complications/*drug therapy/virology
MH  - Ribavirin/blood/*pharmacokinetics/pharmacology
MH  - Severity of Illness Index
PMC - PMC3837852
EDAT- 2013/10/02 06:00
MHDA- 2014/12/23 06:00
PMCR- 2014/06/01
CRDT- 2013/10/02 06:00
PHST- 2013/10/02 06:00 [entrez]
PHST- 2013/10/02 06:00 [pubmed]
PHST- 2014/12/23 06:00 [medline]
PHST- 2014/06/01 00:00 [pmc-release]
AID - AAC.00608-13 [pii]
AID - 00608-13 [pii]
AID - 10.1128/AAC.00608-13 [doi]
PST - ppublish
SO  - Antimicrob Agents Chemother. 2013 Dec;57(12):6097-105. doi: 10.1128/AAC.00608-13. 
      Epub 2013 Sep 30.