title: The pharmacokinetics of peginterferon lambda-1a following single dose administration to subjects with impaired renal function.
abstract: OBJECTIVE
  This open label study was conducted to assess the effect of renal impairment (RI) on the pharmacokinetics (PK) of peginterferon lambda-1a (Lambda).
  
  
  METHODS
  Subjects (age 18-75 years, BMI 18-35 kg m(-2) ) were enrolled into one of five renal function groups: normal (n = 12), mild RI (n = 8), moderate RI (n = 8), severe RI (n = 7), end-stage renal disease (ESRD, n = 8) based on estimated glomerular filtration rate (eGFR) calculated using the Modification of Diet in Renal Disease (MDRD) equation. Subjects received a single dose of Lambda (180 µg) subcutaneously on day 1 followed by PK serum sample collections through day 29. Safety, tolerability and immunogenicity data were collected through day 43. PK parameters were estimated and summarized by group. Geometric mean ratios (GMR) and 90% confidence intervals (CIs) were calculated between normal and RI groups.
  
  
  RESULTS
  With decreasing eGFR, Lambda exposure (Cmax , AUC) increased while apparent clearance (CL/F) and apparent volume of distribution (V/F) decreased. Relative to subjects with normal renal function (geometric mean AUC = 99.5 ng ml(-1) h), Lambda exposure estimates (AUC) were slightly increased in the mild RI group (geometric mean [90% CI]: 1.20 [0.82, 1.77]) and greater in the moderate (1.95 [1.35, 2.83]), severe RI (1.95 [1.30, 2.93]) and ESRD (1.88 [1.30, 2.73]) groups. Lambda was generally well tolerated.
  
  
  CONCLUSIONS
  The results demonstrated that RI reduces the clearance of Lambda and suggests that dose modifications may not be required in patients with mild RI but may be required in patients with moderate to severe RI or ESRD.
authors: Bristol-Myers Squibb Research and Development, Princeton, NJ, USA.
authors: Matthew W
authors: MW
authors: Hruska
authors: Bristol-Myers Squibb Research and Development, Princeton, NJ, USA.
authors: Robert
authors: R
authors: Adamczyk
authors: Bristol-Myers Squibb Research and Development, Princeton, NJ, USA.
authors: Elizabeth
authors: E
authors: Colston
authors: Bristol-Myers Squibb Research and Development, Princeton, NJ, USA.
authors: Michael
authors: M
authors: Hesney
authors: Bristol-Myers Squibb Research and Development, Princeton, NJ, USA.
authors: Michele
authors: M
authors: Stonier
authors: Bristol-Myers Squibb Research and Development, Princeton, NJ, USA.
authors: Heather
authors: H
authors: Myler
authors: Bristol-Myers Squibb Research and Development, Princeton, NJ, USA.
authors: Richard
authors: R
authors: Bertz
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D005919:Glomerular Filtration Rate / Q000187:drug effects*; D006801:Humans; D007378:Interleukins / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000503:physiopathology; D016014:Linear Models; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D012720:Severity of Illness Index; D055815:Young Adult; D000095022:Interferon Lambda
chemical_list: D000998:Antiviral Agents; D007378:Interleukins; D011092:Polyethylene Glycols; C000600496:peginterferon lambda-1a; D000095022:Interferon Lambda
keywords: peginterferon lambda-1a; pharmacokinetics; renal impairment