Potassium canrenoate treatment in paediatric patients: a population pharmacokinetic study using novel dried blood spot sampling

Maysa Suyagh, Ahmed F Hawwa, Paul S Collier, Jeffrey S Millership, Prashant Kole, Muriel Millar, Mike D Shields, Henry L Halliday, James C McElnay

Research output: Contribution to journalArticle

4 Citations (Scopus)

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)0.75?×?e [0.066?×? (PMA?-?40]) and V/F (l)?=?603.30?×? (WT/70)?×?(GA/40)1.89 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).

Conclusion: 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.
Original languageEnglish
Pages (from-to)1901-1908
Number of pages8
JournalJournal of Hypertension
Volume31
Issue number9
DOIs
Publication statusPublished - 10 Jul 2013

Fingerprint Dive into the research topics of 'Potassium canrenoate treatment in paediatric patients: a population pharmacokinetic study using novel dried blood spot sampling'. Together they form a unique fingerprint.

  • Cite this