Pharmacokinetics of oral spironolactone in infants up to 2 years of age.
Purpose: Spironolactone is a potassium sparing diuretic used for decades. Until now, pharmacokinetic (PK) studies of spironolactone have not been conducted in infants and therefore pediatric dosing is based on expert opinion. We aimed to describe the PK profiles of spironolactone and its main metabo...
| Publicado en: | European Journal of Clinical Pharmacology Vol. 80; no. 2; pp. 239 - 249 |
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| Autores principales: | , , , , , , , , , , , , |
| Formato: | research tables/charts Journal Article |
| Publicado: |
Springer Nature
Feb2024
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=175280741&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 175280741 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 00316970 NP9 jtl: European Journal of Clinical Pharmacology issn: 00316970 maglogo: N pubinfo: dt: Feb2024 vid: 80 iid: 2 pid: 237 pub: Springer Nature place: New York, New York artinfo: ui: 175280741 173919443 175280741 175280741 10.1007/s00228-023-03599-w 175280741 ppf: 239 ppct: 10 formats: fmt: – @attributes: type: T – @attributes: type: P tig: atl: Pharmacokinetics of oral spironolactone in infants up to 2 years of age. aug: au: Lass, Jana Leroux, Stephanie Kõrgvee, Lenne-Triin Varendi, Heili Kipper, Karin Takkis, Kalev Aro, Rudolf Metsvaht, Tuuli Oselin, Kersti Pfister, Marc Soeorg, Hiie van den Anker, Johannes Lutsar, Irja affil: https://ror.org/03z77qz90 Institute of Pharmacy, University of Tartu, Tartu, Estonia sug: subj: Spironolactone Pharmacokinetics Administration, Oral Metabolites Steroids Pharmacokinetics Human Infant, Newborn Infant Prospective Studies Chromatography, High Pressure Liquid Mass Spectrometry Body Weight Pediatric Care Heart Failure Edema Drugs, Prescription Descriptive Statistics Data Analysis Software Funding Source Spironolactone Blood Steroids Blood Ascites Infant, Newborn: birth-1 month Infant: 1-23 months ab: Purpose: Spironolactone is a potassium sparing diuretic used for decades. Until now, pharmacokinetic (PK) studies of spironolactone have not been conducted in infants and therefore pediatric dosing is based on expert opinion. We aimed to describe the PK profiles of spironolactone and its main metabolites (7alpha-thiomethylspironolactone (TMS) and canrenone (CAN)) in infants up to two years of age. Methods: The PK of spironolactone and its main metabolites were evaluated following an oral administration of spironolactone (1 mg/kg/dose) to pediatric patients with chronic heart failure, ascites, and/or oedema. The plasma concentration of spironolactone and metabolites (TMS and CAN) was determined using an ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS). Based on rich sampling PK data, the estimation of population PK parameters was performed using nonlinear mixed‐effects modelling software Monolix 2018R2. Results: A total of 150 spironolactone, 158 TMS, and 158 CAN concentrations from 23 patients (ages: 3 days–21 months; median weight 4.3 kg (2.2–12.6)) were available for PK analysis. A one-compartment model for spironolactone, TMS, and CAN best fitted the data. The median (range) of individual estimated apparent clearance values were 47.7 (11.9–138.1) L/h for spironolactone, 9.7 (1.5–66.9) L/h for TMS, and 1.0 (0.2–5.9) L/h for CAN. The disposition of spironolactone and metabolites was mainly affected by size of the patient: body weight explained 22% of inter-individual variability of spironolactone clearance. None of the undesirable effects of spironolactone was documented during the study period. Conclusion: The pharmacokinetics of spironolactone and its metabolites was highly variable between patients below 2 years of age. Body weight explained a significant part of this variability; this highlights the need to take it into account for dosing prescription in this population. (Clinical trial Registration Number 2013–001189-40). pubtype: Academic Journal doctype: research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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