title: A Population Pharmacokinetic Model for51Cr EDTA to Estimate Renal Function.
abstract: 51Cr EDTA clearance (CL) from plasma is used to estimate glomerular filtration rate (GFR). We propose that current methods for analysing the raw51Cr EDTA measurements over-simplifies the disposition of51Cr EDTA and therefore could produce biased GFR estimates. The aim of this study was to develop a population pharmacokinetic model for51Cr EDTA disposition and to compare model-predicted GFR to other methods of estimating renal function.
  
  
  
  Data from 40 individuals who received ~7.4 MBq of51Cr EDTA, as an intravenous bolus, were available for analysis. Plasma radioactivity (counts/min) was measured from timed collection points at 2, 4, 6 and 24 h after the dose. A population analysis was conducted using NONMEM®version 7.2. Model-predicted GFR was compared with other methods for estimating renal function using mean prediction error (MPE).
  
  
  
  A two-compartment pharmacokinetic model with first-order elimination best fit the data. Compared with the model predictions, creatinine CL from 24 h urine data was unbiased. The commonly used 'slope-intercept' method for estimating isotopic GFR was positively biased compared with the model (MPE 15.5 mL/min/1.73 m2[95% confidence interval {CI} 8.9-22.2]. The Cockcroft Gault, Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-Epi) equations led to negatively biased GFR estimates (MPE -19.0 [95% CI -25.4 to -12.7], -20.1 [95% CI -27.2 to -13.1] and -16.5 [95% CI -22.2 to -10.1] mL/min/1.73 m2, respectively).
  
  
  
  The biased GFR estimates were most obvious in patients with relatively normal renal function. This may lead to inaccurate dosing in patients who are receiving drugs with a narrow therapeutic range where dosing is adjusted according to GFR estimates (e.g. carboplatin).
  
  
  
  The study is registered with the Australian New Zealand Clinical Trials Registry (ANZCTR), number: ACTRN 12611000035921.
authors.affiliation: School of Pharmacy, University of Otago, PO Box 56, Dunedin, 9054, New Zealand.
authors.forename: Isabelle H S
authors.initials: IHS
authors.lastname: Kuan
authors.affiliation: School of Pharmacy, University of Otago, PO Box 56, Dunedin, 9054, New Zealand.
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Duffull
authors.affiliation: Department of Medicine, University of Otago, Dunedin, New Zealand.
authors.forename: Tracey L
authors.initials: TL
authors.lastname: Putt
authors.affiliation: Department of Medicine, University of Otago, Dunedin, New Zealand.
authors.forename: John B W
authors.initials: JBW
authors.lastname: Schollum
authors.affiliation: Department of Medicine, University of Otago, Dunedin, New Zealand.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Walker
authors.affiliation: School of Pharmacy, University of Otago, PO Box 56, Dunedin, 9054, New Zealand. dan.wright@otago.ac.nz.
authors.forename: Daniel F B
authors.initials: DFB
authors.lastname: Wright
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002860:Chromium Radioisotopes; D004492:Edetic Acid / Q000097:blood / Q000493:pharmacokinetics*; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007668:Kidney / Q000502:physiology*; D007674:Kidney Diseases / Q000097:blood / Q000503:physiopathology; D008297:Male; D008954:Models, Biological; D055815:Young Adult
chemical_list: D002860:Chromium Radioisotopes; D004492:Edetic Acid