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POPULATION PHARMACOKINETICS OF INTRAVENOUS ALBUTEROL IN CHILDREN WITH STATUS ASTHMATICUS
  1. Nienke J Vet1,
  2. Brenda CM de Winter2,
  3. Saskia N de Wildt1,
  4. Bart CH van der Nagel2,
  5. Catherijne AJ Knibbe3,
  6. Muriel Koninckx4,
  7. Matthijs de Hoog1,
  8. Birgit CP Koch2
  1. 1Intensive Care, Erasmus MC Sophia Children's Hospital, Rotterdam. The Netherlands
  2. 2Department of hospital pharmacy, Erasmus Medical Center, Rotterdam, The Netherlands
  3. 3Division of Pharmacology, LACDR, Leiden University, Leiden, the Netherlands
  4. 4Paediatric Intensive Care, Middelheim Ziekenhuis, Antwerp, Belgium

Abstract

Objectives To develop a population pharmacokinetic model of R-albuterol and S-albuterol for children suffering from status asthmaticus following continuous intravenous administration.

Methods At the pediatric ICU 19 children suffering from severe status asthmaticus were treated using continuous intravenous albuterol in doses based on clinical symptoms (range 0.1–10 µg/kg/min). During therapy 111 blood samples were collected and analysed for R- and S-albuterol using a validated LC/MS-MS method. A population pharmacokinetic analysis was conducted using non-linear mixed effects modelling (NONMEM 7.2). Data was logarithmically transformed. Model selection criteria were decrease in objective function, diagnostic plots and NPDE. The covariates (range) analysed were bodyweight (7.8–70 kg), age (0.8–15.3 years), creatinine concentration (17–70 µmol/L), alanine transaminase (5–29 IU/L), and urea (1.6–4.8 mmol/L).

Results A two-compartment model with separated clearance for R- (16.3 L/h) and S-albuterol (8.8 L/h) best described the data. Separated values for central volume of distribution (12.9 L), peripheral volume of distribution (45.2 L) and intercompartmental clearance (20.0 L/h) did not improve the model. Between-subject variability was described for clearance of R-albuterol (42%), clearance of S-albuterol (37%) and central volume of distribution (280%). Weight is a significant covariate using a power function. The exponent of the powerfunction was fixed at 0.75 for clearance and intercompartmental and at 1 for central and peripheral volume of distribution. Estimation of the exponent resulted in similar values and did not improve the model. No other covariates were identified.

Conclusion The population pharmacokinetics of R- and S-albuterol are described. This model can be used to evaluate the correlation between albuterol pharmacokinetics and effect in a population pharmacokinetic-pharmacodynamic analysis.

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