title: Effects of renal insufficiency on the elimination of fluorescein lisicol (NRL972), an investigational marker of hepatic transporter function.
abstract: BACKGROUND
  NRL972 (Fluorescein Lisicol), a fluorescent-labelled bile salt, is an investigational marker of hepatic biliary transporter function.
  
  
  OBJECTIVE
  To investigate the pharmacokinetics (PK) of NRL972 in patients with severe (SRI: creatinine clearance (CLCr)<30 mL/min per 1.73 m2 body surface area (BSA)) and mild-to-moderate renal insufficiency (MRI: 30≤CLCr<80 mL/min) relative to matched controls (CON: CLCr≥90 mL/min).
  
  
  METHODS
  The plasma and urinary PK of NRL972 were determined after single 2-mg doses of NRL972 administered by 15-second intravenous (IV) injection. The PK were derived noncompartmentally using all data points up to 6 hours after dosing or only using the concentrations at 10 and 30 minutes after injection.
  
  
  RESULTS
  17, 22, and 16 subjects were enrolled in the SRI, MRI, and CON group, respectively. NRL972 was hardly quantifiable in urine in any of the subjects groups. The plasma concentrations of NRL972 declined rapidly after dosing in mostly monoexponential fashion. The decline tended to be faster in patients with renal insufficiency: in SRI patients, the point and 95% confidence interval (CI) estimates of the group ratios (SRI/CON) were 0.691 (CI: 0.517 to 0.925) for the C(30):C(10) concentration ratio, 0.785 (CI: 0.634 to 0.970) for t1/2, and 1.344 (CI: 1.028 to 1.757) for bodyweight normalized clearance (CL/BW); in MRI patients, the effect was slightly less.
  
  
  CONCLUSIONS
  Renal insufficiency does not impair the elimination of NRL972; instead, there is a trend of enhanced NRL972 disposition in patients with compromised renal function. Concomitant renal impairment is unlikely to have confounding effects on the evaluation of hepatic function by NRL972 testing.
authors.forename: Christian
authors.initials: C
authors.lastname: de Mey
authors.forename: Emil
authors.initials: E
authors.lastname: Gatchev
authors.forename: Boriana
authors.initials: B
authors.lastname: Deliyska
mesh_terms: D000328:Adult; D001692:Biological Transport; D015415:Biomarkers / Q000097:blood / Q000652:urine; D003404:Creatinine / Q000652:urine; D005260:Female; D005452:Fluoresceins / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005456:Fluorescent Dyes / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006801:Humans; D007275:Injections, Intravenous; D008099:Liver / Q000378:metabolism*; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D011446:Prospective Studies; D051437:Renal Insufficiency / Q000175:diagnosis / Q000378:metabolism*; D012720:Severity of Illness Index; D055815:Young Adult
chemical_list: D015415:Biomarkers; D005452:Fluoresceins; D005456:Fluorescent Dyes; C000601594:NRL972; D003404:Creatinine