Quetiapine dose optimisation during gestation: a pharmacokinetic modelling study

Raj K.S. Badhan*, Hannah Macfarlane

*Corresponding author for this work

Research output: Contribution to journalArticle

Abstract

Objectives: The second-generation antipsychotic quetiapine has been demonstrated to undergo gestation-related changes in pharmacokinetics. This study applied pharmacokinetic modelling principles to investigate the mechanism of these changes and to propose new dosing strategies to counteract these changes. Methods: A pharmacokinetic modelling approach was implemented using virtual population groups. Changes in quetiapine trough plasma concentration during gestation were quantified across all trimesters, and dose adjustment strategies were applied to counteract these changes by targeting a therapeutic range of 50–500 ng/ml throughout gestation. Key findings: The application of the model during gestation predicted a decrease in trough concentration. A maximum decrease of 58% was predicted during trimester 2, and being associated with a statistically significant decrease in oral clearance at gestation week 25, 204 l/h ± 100.8 l/h compared with non-pregnant subjects, 121.9 l/h ± 51.8 l/h. A dosing optimisation strategy identified that dose increases to 500–700 mg twice daily would result in 32–55% of subjects possessing trough concentration in excess of 50 ng/ml. Conclusions: Quetiapine doses in pregnancy should be increased to 500–700 mg twice daily to counteract a concomitant increase in metabolic clearance, increase in volume of distribution and decrease in plasma protein binding.

Original languageEnglish
Pages (from-to)670-681
Number of pages12
JournalJournal of Pharmacy and Pharmacology
Volume72
Issue number5
Early online date3 Feb 2020
DOIs
Publication statusPublished - 1 May 2020

Bibliographical note

This is the peer reviewed version of the following article: Badhan, R.K.S. and Macfarlane, H. (2020), Quetiapine dose optimisation during gestation: a pharmacokinetic modelling study. J Pharm Pharmacol., which has been published in final form at https://doi.org/10.1111/jphp.13236.  This article may be used for non-commercial purposes in accordance With Wiley Terms and Conditions for self-archiving.

Keywords

  • dose optimisation
  • pharmacokinetics
  • physiologically-based pharmacokinetics
  • pregnancy
  • quetiapine

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