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Population pharmacokinetics of olanzapine in children.

Publication ,  Journal Article
Maharaj, AR; Wu, H; Zimmerman, KO; Autmizguine, J; Kalra, R; Al-Uzri, A; Sherwin, CMT; Goldstein, SL; Watt, K; Erinjeri, J; Payne, EH ...
Published in: Br J Clin Pharmacol
February 2021

AIMS: The aim of this study was to evaluate the population pharmacokinetics (PopPK) of olanzapine in children and devise a model-informed paediatric dosing scheme. METHODS: The PopPK of olanzapine was characterized using opportunistically collected plasma samples from children receiving olanzapine per standard of care for any indication. A nonlinear mixed effect modelling approach was employed for model development using the software NONMEM (v7.4). Simulations from the developed PopPK model were used to devise a paediatric dosing scheme that targeted comparable plasma exposures to adolescents and adults. RESULTS: Forty-five participants contributed 83 plasma samples towards the analysis. The median (range) postnatal age and body weight of participants were 3.8 years (0.2-19.2) and 14.1 kg (4.2-111.7), respectively. The analysis was restricted to pharmacokinetic (PK) samples collected following enteral administration (oral and feeding tube). A one-compartment model with linear elimination provided an appropriate fit to the data. The final model included the covariates body weight and postmenstrual age (PMA) on apparent olanzapine clearance (CL/F). Typical CL/F and apparent volume of distribution (scaled to 70 kg) were 16.8 L/h (21% RSE) and 663 L (13% RSE), respectively. Developed dosing schemes used weight-normalized doses for children ≤6 months postnatal age or <15 kg and fixed doses for children ≥15 kg. CONCLUSION: We developed a paediatric PopPK model for enterally-administered olanzapine. To our knowledge, this analysis is the first study to characterize the PK of olanzapine in participants ranging from infants to adolescents. Body weight and PMA were identified as influential covariates for characterizing developmental changes in olanzapine apparent clearance.

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Published In

Br J Clin Pharmacol

DOI

EISSN

1365-2125

Publication Date

February 2021

Volume

87

Issue

2

Start / End Page

542 / 554

Location

England

Related Subject Headings

  • Pharmacology & Pharmacy
  • Olanzapine
  • Nonlinear Dynamics
  • Models, Biological
  • Infant
  • Humans
  • Child
  • Adult
  • Adolescent
  • 3214 Pharmacology and pharmaceutical sciences
 

Citation

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Maharaj, A. R., Wu, H., Zimmerman, K. O., Autmizguine, J., Kalra, R., Al-Uzri, A., … Hornik, C. P. (2021). Population pharmacokinetics of olanzapine in children. Br J Clin Pharmacol, 87(2), 542–554. https://doi.org/10.1111/bcp.14414
Maharaj, Anil R., Huali Wu, Kanecia O. Zimmerman, Julie Autmizguine, Rohit Kalra, Amira Al-Uzri, Catherine M. T. Sherwin, et al. “Population pharmacokinetics of olanzapine in children.Br J Clin Pharmacol 87, no. 2 (February 2021): 542–54. https://doi.org/10.1111/bcp.14414.
Maharaj AR, Wu H, Zimmerman KO, Autmizguine J, Kalra R, Al-Uzri A, et al. Population pharmacokinetics of olanzapine in children. Br J Clin Pharmacol. 2021 Feb;87(2):542–54.
Maharaj, Anil R., et al. “Population pharmacokinetics of olanzapine in children.Br J Clin Pharmacol, vol. 87, no. 2, Feb. 2021, pp. 542–54. Pubmed, doi:10.1111/bcp.14414.
Maharaj AR, Wu H, Zimmerman KO, Autmizguine J, Kalra R, Al-Uzri A, Sherwin CMT, Goldstein SL, Watt K, Erinjeri J, Payne EH, Cohen-Wolkowiez M, Hornik CP. Population pharmacokinetics of olanzapine in children. Br J Clin Pharmacol. 2021 Feb;87(2):542–554.
Journal cover image

Published In

Br J Clin Pharmacol

DOI

EISSN

1365-2125

Publication Date

February 2021

Volume

87

Issue

2

Start / End Page

542 / 554

Location

England

Related Subject Headings

  • Pharmacology & Pharmacy
  • Olanzapine
  • Nonlinear Dynamics
  • Models, Biological
  • Infant
  • Humans
  • Child
  • Adult
  • Adolescent
  • 3214 Pharmacology and pharmaceutical sciences