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

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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

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Canrenoic Acid
Canrenone
Pharmacokinetics
Pediatrics
Weights and Measures
Population
Gestational Age
Therapeutics
Lung Diseases
Half-Life
Chronic Disease
Heart Failure

Cite this

Suyagh, Maysa ; Hawwa, Ahmed F ; Collier, Paul S ; Millership, Jeffrey S ; Kole, Prashant ; Millar, Muriel ; Shields, Mike D ; Halliday, Henry L ; McElnay, James C. / Potassium canrenoate treatment in paediatric patients: a population pharmacokinetic study using novel dried blood spot sampling. In: Journal of Hypertension. 2013 ; Vol. 31, No. 9. pp. 1901-1908.
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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.",
author = "Maysa Suyagh and Hawwa, {Ahmed F} and Collier, {Paul S} and Millership, {Jeffrey S} and Prashant Kole and Muriel Millar and Shields, {Mike D} and Halliday, {Henry L} and McElnay, {James C}",
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Potassium canrenoate treatment in paediatric patients: a population pharmacokinetic study using novel dried blood spot sampling. / Suyagh, Maysa; Hawwa, Ahmed F; Collier, Paul S; Millership, Jeffrey S; Kole, Prashant; Millar, Muriel; Shields, Mike D; Halliday, Henry L; McElnay, James C.

In: Journal of Hypertension, Vol. 31, No. 9, 10.07.2013, p. 1901-1908.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Potassium canrenoate treatment in paediatric patients: a population pharmacokinetic study using novel dried blood spot sampling

AU - Suyagh, Maysa

AU - Hawwa, Ahmed F

AU - Collier, Paul S

AU - Millership, Jeffrey S

AU - Kole, Prashant

AU - Millar, Muriel

AU - Shields, Mike D

AU - Halliday, Henry L

AU - McElnay, James C

PY - 2013/7/10

Y1 - 2013/7/10

N2 - 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.

AB - 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.

U2 - 10.1097/HJH.0b013e3283626994

DO - 10.1097/HJH.0b013e3283626994

M3 - Article

C2 - 23846862

VL - 31

SP - 1901

EP - 1908

JO - Journal of Hypertension

JF - Journal of Hypertension

SN - 0263-6352

IS - 9

ER -