title: Potassium canrenoate treatment in paediatric patients: a population pharmacokinetic study using novel dried blood spot sampling.
abstract: OBJECTIVE
  To characterize the population pharmacokinetics of canrenone following administration of potassium canrenoate (K-canrenoate) in paediatric patients.
  
  
  METHODS
  Data were collected prospectively from 37 paediatric patients (median weight 2.9 kg, age range 2 days-0.85 years) who received intravenous K-canrenoate for management of retained fluids, for example in heart failure and chronic lung disease. Dried blood spot (DBS) samples (n=213) from these were analysed for canrenone content and the data subjected to pharmacokinetic analysis using nonlinear mixed-effects modelling. Another group of patients (n=16) who had 71 matching plasma and DBS samples was analysed separately to compare canrenone pharmacokinetic parameters obtained using the two different matrices.
  
  
  RESULTS
  A one-compartment model best described the DBS data. Significant covariates were weight, postmenstrual age (PMA) and gestational age. The final population models for canrenone clearance (CL/F) and volume of distribution (V/F) in DBS were CL/F (l/h) = 12.86 ×  (WT/70.0) × e [0.066 ×  (PMA - 40]) and V/F (l) = 603.30 ×  (WT/70) × (GA/40) where weight is in kilograms. The corresponding values of CL/F and V/F in a patient with a median weight of 2.9 kg are 1.11 l/h and 20.48 l, respectively. Estimated half-life of canrenone based on DBS concentrations was similar to that based on matched plasma concentrations (19.99 and 19.37 h, respectively, in 70 kg patient).
  
  
  CONCLUSIONS
  The range of estimated CL/F in DBS for the study population was 0.12-9.62 l/h; hence, bodyweight-based dosage adjustment of K-canrenoate appears necessary. However, a dosing scheme that takes into consideration both weight and age (PMA/gestational age) of paediatric patients seems more appropriate.
authors.affiliation: aClinical & Practice Research Group, School of Pharmacy bRegional Neonatal Unit, Royal Maternity Hospital and Department of Child Health cRoyal Belfast Hospital for Sick Children, Belfast Health and Social Care Trust and Institute of Clinical Research, Queen's University Belfast, 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; D001835:Body Weight; D002191:Canrenoic Acid / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D003198:Computer Simulation; D059788:Dried Blood Spot Testing / Q000379:methods*; D004334:Drug Administration Schedule; D005260:Female; D005865:Gestational Age; D006333:Heart Failure / Q000097:blood / Q000188:drug therapy; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008171:Lung Diseases / Q000097:blood / Q000188:drug therapy; D008297:Male; D011446:Prospective Studies; D016896:Treatment Outcome
chemical_list: D002191:Canrenoic Acid