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A pharmacokinetic model for amiodarone in infants developed from an opportunistic sampling trial and published literature data.

Publication ,  Journal Article
Dallefeld, SH; Atz, AM; Yogev, R; Sullivan, JE; Al-Uzri, A; Mendley, SR; Laughon, M; Hornik, CP; Melloni, C; Harper, B; Lewandowski, A; Wu, H ...
Published in: J Pharmacokinet Pharmacodyn
June 2018

Amiodarone is a first-line antiarrhythmic for life-threatening ventricular fibrillation or ventricular tachycardia in children, yet little is known about its pharmacokinetics (PK) in this population. We developed a population PK (PopPK) model using samples collected via an opportunistic study design of children receiving amiodarone per standard of care supplemented by amiodarone PK data from the literature. Both study data and literature data were predominantly from infants < 2 years old, so our analysis was restricted to this group. The final combined dataset consisted of 266 plasma drug concentrations in 45 subjects with a median (interquartile range) postnatal age of 40.1 (11.0-120.4) days and weight of 3.9 (3.1-5.1) kg. Since the median sampling time after the first dose was short (study: 95 h; literature: 72 h) relative to the terminal half-life estimated in adult PopPK studies, values of the deep compartment volume and flow were fixed to literature values. A 3-compartment model best described the data and was validated by visual predictive checks and non-parametric bootstrap analysis. The final model included body weight as a covariate on all volumes and on both inter-compartmental and elimination clearances. The empiric Bayesian estimates for clearance (CL), volume of distribution at steady state, and terminal half-life were 0.25 (90% CL 0.14-0.36) L/kg/h, 93 (68-174) L/kg, and 266 (197-477) h, respectively. These studies will provide useful information for future PopPK studies of amiodarone in infants and children that could improve dosage regimens.

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Published In

J Pharmacokinet Pharmacodyn

DOI

EISSN

1573-8744

Publication Date

June 2018

Volume

45

Issue

3

Start / End Page

419 / 430

Location

United States

Related Subject Headings

  • Prospective Studies
  • Pharmacology & Pharmacy
  • Models, Biological
  • Male
  • Infant, Newborn
  • Infant
  • Humans
  • Half-Life
  • Female
  • Dose-Response Relationship, Drug
 

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Dallefeld, S. H., Atz, A. M., Yogev, R., Sullivan, J. E., Al-Uzri, A., Mendley, S. R., … Cohen-Wolkowiez, M. (2018). A pharmacokinetic model for amiodarone in infants developed from an opportunistic sampling trial and published literature data. J Pharmacokinet Pharmacodyn, 45(3), 419–430. https://doi.org/10.1007/s10928-018-9576-y
Dallefeld, Samantha H., Andrew M. Atz, Ram Yogev, Janice E. Sullivan, Amira Al-Uzri, Susan R. Mendley, Matthew Laughon, et al. “A pharmacokinetic model for amiodarone in infants developed from an opportunistic sampling trial and published literature data.J Pharmacokinet Pharmacodyn 45, no. 3 (June 2018): 419–30. https://doi.org/10.1007/s10928-018-9576-y.
Dallefeld SH, Atz AM, Yogev R, Sullivan JE, Al-Uzri A, Mendley SR, et al. A pharmacokinetic model for amiodarone in infants developed from an opportunistic sampling trial and published literature data. J Pharmacokinet Pharmacodyn. 2018 Jun;45(3):419–30.
Dallefeld, Samantha H., et al. “A pharmacokinetic model for amiodarone in infants developed from an opportunistic sampling trial and published literature data.J Pharmacokinet Pharmacodyn, vol. 45, no. 3, June 2018, pp. 419–30. Pubmed, doi:10.1007/s10928-018-9576-y.
Dallefeld SH, Atz AM, Yogev R, Sullivan JE, Al-Uzri A, Mendley SR, Laughon M, Hornik CP, Melloni C, Harper B, Lewandowski A, Mitchell J, Wu H, Green TP, Cohen-Wolkowiez M. A pharmacokinetic model for amiodarone in infants developed from an opportunistic sampling trial and published literature data. J Pharmacokinet Pharmacodyn. 2018 Jun;45(3):419–430.
Journal cover image

Published In

J Pharmacokinet Pharmacodyn

DOI

EISSN

1573-8744

Publication Date

June 2018

Volume

45

Issue

3

Start / End Page

419 / 430

Location

United States

Related Subject Headings

  • Prospective Studies
  • Pharmacology & Pharmacy
  • Models, Biological
  • Male
  • Infant, Newborn
  • Infant
  • Humans
  • Half-Life
  • Female
  • Dose-Response Relationship, Drug