title: A systematic comparison of cockcroft-gault and modification of diet in renal disease equations for classification of kidney dysfunction and dosage adjustment.
abstract: BACKGROUND
  The dosing of drugs in patients with kidney dysfunction is often based on the estimates of kidney function.
  
  
  OBJECTIVE
  To systematically compare the performance of the Modification of Diet in Renal Disease (MDRD) and Cockcroft-Gault (CG) equations for dosage adjustment.
  
  
  METHODS
  We assessed agreement (concordance, kappa statistics [κ,κ(ω)]) between CG and MDRD using a Food and Drug Administration database to evaluate the effect of renal function on the pharmacokinetics of 36 approved drugs. Across the approved drugs, we compared the correlation between these 2 equations for renal drug clearance (Cl(ren)) and area under the concentration-time curve. For 26 approved drugs that require renal dose adjustment, we also compared dosing regimens and expected exposure using these equations. Sensitivity analyses were performed by adjusting the MDRD estimates for individualized body surface area and/or range of serum creatinine assay calibration errors.
  
  
  RESULTS
  In the pharmacokinetic database with 973 subjects (age 18-95 years, weight 35-153 kg, female 33%), we found that the CG and the MDRD classification of renal function generally agreed (64.2%, κ = 0.54, κ(ω) = 0.73). Among the subjects studied for drugs requiring renal dose adjustment, dosages in 12% were changed to a higher or lower dosing category by the MDRD compared to the CG equation. In particular, using MDRD in place of CG for dosage modification yielded higher dosing recommendations for subjects with a combination of age >80 years, weight <55 kg, and serum creatinine >0.7 and ≤1.5 mg/dL; the coefficient of determination was also higher by CG than MDRD in trials that enrolled these or similar patients.
  
  
  CONCLUSIONS
  For patients with advanced age, low weight, and modestly elevated serum creatinine, further work is needed before the MDRD equations can replace the CG equation for dose adjustment in the labeling.
authors.affiliation: Division of Cardiovascular and Renal Products, Office of New Drugs, Center for Drug Evaluation and Research, United States Food and Drug Administration (FDA), Silver Spring, MD, USA.
authors.forename: Eun Jung
authors.initials: EJ
authors.lastname: Park
authors.forename: Kunyi
authors.initials: K
authors.lastname: Wu
authors.forename: Zenghui
authors.initials: Z
authors.lastname: Mi
authors.forename: Ting
authors.initials: T
authors.lastname: Dong
authors.forename: John P
authors.initials: JP
authors.lastname: Lawrence
authors.forename: Chia-Wen
authors.initials: CW
authors.lastname: Ko
authors.forename: Shiew-Mei
authors.initials: SM
authors.lastname: Huang
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.forename: Victor
authors.initials: V
authors.lastname: Crentsil
authors.forename: Jialu
authors.initials: J
authors.lastname: Zhang
authors.forename: Nancy N
authors.initials: NN
authors.lastname: Xu
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D019540:Area Under Curve; D016208:Databases, Factual; D004032:Diet; D054796:Drug Dosage Calculations; D005260:Female; D006801:Humans; D007668:Kidney / Q000502:physiology; D007674:Kidney Diseases / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D004364:Pharmaceutical Preparations / Q000008:administration & dosage* / Q000378:metabolism; D010599:Pharmacokinetics; D014481:United States; D014486:United States Food and Drug Administration; D055815:Young Adult
chemical_list: D004364:Pharmaceutical Preparations