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Comparative Study
. 2020 Aug;72(8):1049-1060.
doi: 10.1111/jphp.13281. Epub 2020 Apr 28.

Precision dosing-based optimisation of paroxetine during pregnancy for poor and ultrarapid CYP2D6 metabolisers: a virtual clinical trial pharmacokinetics study

Aminah Almurjan  1 , Hannah Macfarlane  1 , Raj K S Badhan  1
Affiliations
Comparative Study

Precision dosing-based optimisation of paroxetine during pregnancy for poor and ultrarapid CYP2D6 metabolisers: a virtual clinical trial pharmacokinetics study

Aminah Almurjan et al. J Pharm Pharmacol. 2020 Aug.

Abstract

Objective: Paroxetine has been demonstrated to undergo gestation-related reductions in plasma concentrations, to an extent which is dictated by the polymorphic state of CYP 2D6. However, knowledge of appropriate dose titrations is lacking.

Methods: A pharmacokinetic modelling approach was applied to examine gestational changes in trough plasma concentrations for CYP 2D6 phenotypes, followed by necessary dose adjustment strategies to maintain paroxetine levels within a therapeutic range of 20-60 ng/ml.

Key findings: A decrease in trough plasma concentrations was simulated throughout gestation for all phenotypes. A significant number of ultrarapid (UM) phenotype subjects possessed trough levels below 20 ng/ml (73-76%) compared to extensive metabolisers (EM) (51-53%).

Conclusions: For all phenotypes studied, there was a requirement for daily doses in excess of the standard 20 mg dose throughout gestation. For EM, a dose of 30 mg daily in trimester 1 followed by 40 mg daily in trimesters 2 and 3 is suggested to be optimal. For poor metabolisers (PM), a 20 mg daily dose in trimester 1 followed by 30 mg daily in trimesters 2 and 3 is suggested to be optimal. For UM, a 40 mg daily dose throughout gestation is suggested to be optimal.

Keywords: paroxetine; pharmacokinetics; phenotype; physiologically based pharmacokinetic; pregnancy.

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References

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