title: Population pharmacokinetic model of canrenone after intravenous administration of potassium canrenoate to paediatric patients.
abstract: BACKGROUND
  Little is known about the pharmacokinetics of potassium canrenoate/canrenone in paediatric patients
  
  
  CONCLUSIONS
  A population pharmacokinetic model has been developed to evaluate the pharmacokinetics of canrenone in paediatric patients who received potassium canrenoate as part of their therapy in the intensive care unit. AIMS To characterize the population pharmacokinetics of canrenone following administration of potassium canrenoate to paediatric patients.
  
  
  METHODS
  Data were collected prospectively from 23 paediatric patients (2 days to 10 years of age; median weight 4 kg, range 2.16-28.0 kg) who received intravenous potassium canrenoate (K-canrenoate) as part of their intensive care therapy for removal of retained fluids, e.g. in pulmonary oedema due to chronic lung disease and for the management of congestive heart failure. Plasma samples were analyzed by HPLC for determination of canrenone (the major metabolite and pharmacologically active moiety) and the data subjected to pharmacokinetic analysis using NONMEM.
  
  
  RESULTS
  A one compartment model best described the data. The only significant covariate was weight (WT). The final population models for canrenone clearance (CL/F) and volume of distribution (V/F) were CL/F (l h(-1) ) = 11.4 × (WT/70.0)(0.75) and V/F (l) = 374.2 × (WT/70) where WT is in kg. The values of CL/F and V/F in a 4 kg child would be 1.33 l h(-1) and 21.4 l, respectively, resulting in an elimination half-life of 11.2 h.
  
  
  CONCLUSIONS
  The range of estimated CL/F in the study population was 0.67-7.38 l h(-1) . The data suggest that adjustment of K-canrenoate dosage according to body weight is appropriate in paediatric patients.
authors.affiliation: Clinical & Practice Research Group, School of Pharmacy, Queen's University Belfast, 97 Lisburn Road, Belfast, UK.
authors.forename: Maysa
authors.initials: M
authors.lastname: Suyagh
authors.forename: Ahmed F
authors.initials: AF
authors.lastname: Hawwa
authors.forename: Paul S
authors.initials: PS
authors.lastname: Collier
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Millership
authors.forename: Prashant
authors.initials: P
authors.lastname: Kole
authors.forename: Muriel
authors.initials: M
authors.lastname: Millar
authors.forename: Mike D
authors.initials: MD
authors.lastname: Shields
authors.forename: Henry L
authors.initials: HL
authors.lastname: Halliday
authors.forename: James C
authors.initials: JC
authors.lastname: McElnay
mesh_terms: D061605:Administration, Intravenous; D002191:Canrenoic Acid / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D002192:Canrenone / Q000493:pharmacokinetics*; D002648:Child; D002675:Child, Preschool; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D003422:Critical Care; D005260:Female; D006207:Half-Life; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D000451:Mineralocorticoid Receptor Antagonists / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D008954:Models, Biological; D017711:Nonlinear Dynamics; D011446:Prospective Studies; D014018:Tissue Distribution
chemical_list: D000451:Mineralocorticoid Receptor Antagonists; D002192:Canrenone; D002191:Canrenoic Acid