Population pharmacokinetic model of canrenone after intravenous administration of potassium canrenoate to paediatric patients

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

Research output: Contribution to journalArticle

Abstract

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT
• Little is known about the pharmacokinetics of potassium canrenoate/canrenone in paediatric patients

WHAT THIS STUDY ADDS
• 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.

Original languageEnglish
Pages (from-to)864-72
Number of pages9
JournalBritish Journal of Clinical Pharmacology
Volume74
Issue number5
Early online date9 Oct 2012
DOIs
Publication statusPublished - Nov 2012

Fingerprint

Canrenoic Acid
Canrenone
Intravenous Administration
Pharmacokinetics
Pediatrics
Weights and Measures
Population
Pulmonary Edema
Critical Care
Disease Management
Lung Diseases
Intensive Care Units
Half-Life
Chronic Disease
Research Design
Heart Failure
High Pressure Liquid Chromatography
Body Weight
Therapeutics

Bibliographical note

© 2012 The Authors. British Journal of Clinical Pharmacology © 2012 The British Pharmacological Society.

Keywords

  • canrenone
  • neonates
  • paediatrics
  • population pharmacokinetics
  • potassium canrenoate

Cite this

Suyagh, Maysa ; Hawwa, Ahmed F. ; Millership, Jeffrey S. ; Collier, Paul S. ; Kole, Prashant ; Millar, Muriel ; Shields, Michael D. ; Halliday, Henry L. ; McElnay, James C. / Population pharmacokinetic model of canrenone after intravenous administration of potassium canrenoate to paediatric patients. In: British Journal of Clinical Pharmacology. 2012 ; Vol. 74, No. 5. pp. 864-72.
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abstract = "WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Little is known about the pharmacokinetics of potassium canrenoate/canrenone in paediatric patients WHAT THIS STUDY ADDS • 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.",
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Suyagh, M, Hawwa, AF, Millership, JS, Collier, PS, Kole, P, Millar, M, Shields, MD, Halliday, HL & McElnay, JC 2012, 'Population pharmacokinetic model of canrenone after intravenous administration of potassium canrenoate to paediatric patients', British Journal of Clinical Pharmacology, vol. 74, no. 5, pp. 864-72. https://doi.org/10.1111/j.1365-2125.2012.04257.x

Population pharmacokinetic model of canrenone after intravenous administration of potassium canrenoate to paediatric patients. / Suyagh, Maysa; Hawwa, Ahmed F.; Millership, Jeffrey S.; Collier, Paul S.; Kole, Prashant; Millar, Muriel; Shields, Michael D.; Halliday, Henry L.; McElnay, James C.

In: British Journal of Clinical Pharmacology, Vol. 74, No. 5, 11.2012, p. 864-72.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Population pharmacokinetic model of canrenone after intravenous administration of potassium canrenoate to paediatric patients

AU - Suyagh, Maysa

AU - Hawwa, Ahmed F.

AU - Millership, Jeffrey S.

AU - Collier, Paul S.

AU - Kole, Prashant

AU - Millar, Muriel

AU - Shields, Michael D.

AU - Halliday, Henry L.

AU - McElnay, James C.

N1 - © 2012 The Authors. British Journal of Clinical Pharmacology © 2012 The British Pharmacological Society.

PY - 2012/11

Y1 - 2012/11

N2 - WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Little is known about the pharmacokinetics of potassium canrenoate/canrenone in paediatric patients WHAT THIS STUDY ADDS • 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.

AB - WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Little is known about the pharmacokinetics of potassium canrenoate/canrenone in paediatric patients WHAT THIS STUDY ADDS • 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.

KW - canrenone

KW - neonates

KW - paediatrics

KW - population pharmacokinetics

KW - potassium canrenoate

UR - http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2125.2012.04257.x/abstract

U2 - 10.1111/j.1365-2125.2012.04257.x

DO - 10.1111/j.1365-2125.2012.04257.x

M3 - Article

C2 - 22376078

VL - 74

SP - 864

EP - 872

JO - British Journal of Clinical Pharmacology

JF - British Journal of Clinical Pharmacology

SN - 0306-5251

IS - 5

ER -