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

作者：Suyagh Maysa; Hawwa Ahmed F; Collier Paul S; Millership Jeffrey S; Kole Prashant; Millar Muriel; Shields Mike D; Halliday Henry L; McElnay James C^*

来源：Journal of Hypertension, 2013, 31(9): 1901-1908.

DOI：10.1097/HJH.0b013e3283626994

• canrenone
• dried blood spots
• neonates
• nonlinear mixed-effect modelling
• population pharmacokinetics
• potassium canrenoate

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 2.9kg, 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)=12.86x (WT/70.0)(0.75)xe [0.066x (PMA-40]) and V/F (l)=603.30x (WT/70)x(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 2.9kg are 1.11l/h and 20.48l, respectively. Estimated half-life of canrenone based on DBS concentrations was similar to that based on matched plasma concentrations (19.99 and 19.37h, respectively, in 70kg patient).Conclusion:The range of estimated CL/F in DBS for the study population was 0.12-9.62l/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.

• 出版日期2013-9