Physiologically based pharmacokinetic modelling predicts altered maternal pharmacokinetics of amitriptyline during pregnancy

Simple item page
dc.check.date2026-05-01en
dc.check.infoAccess to this article is restricted until 12 months after publication by request of the publisheren
dc.contributor.authorScherf‐Clavel, Maikeen
dc.contributor.authorLeutritz, Anna Lindaen
dc.contributor.authorGehrmann, Andreaen
dc.contributor.authorUnterecker, Stefanen
dc.contributor.authorWalther, Sebastianen
dc.contributor.authorKittel‐Schneider, Sarahen
dc.contributor.funderInterdisciplinary Center for Clinical Researchen
dc.date.accessioned2025-05-21T16:01:53Z
dc.date.available2025-05-21T16:01:53Z
dc.date.issued2025-05-01en
dc.description.abstractAims: Pharmacotherapy of maternal peripartum depression is an increasing challenge. Amitriptyline (AMI) is the most often used tricyclic antidepressant during pregnancy, but knowledge on pharmacokinetics in this special phase is lacking. Physiologically based pharmacokinetic (PBPK) modelling is a powerful tool to better understand pregnancy-induced pharmacokinetic changes of medication. We aimed to improve the knowledge about AMI pharmacokinetics during pregnancy using PBPK modelling. Consequently, we aimed to add new information for an effective and safe pharmacotherapy in pregnant women. Methods: A PBPK model, including AMI, but also its active metabolite nortriptyline (NOR), was developed to investigate pregnancy-induced pharmacokinetic changes after AMI administration. The predicted drug exposure was compared to observed concentrations in pregnant patients in clinical routine. The PBPK model was set up using PK-Sim Version 11. Results: Serum concentration profiles were described successfully. During pregnancy, active moiety serum concentration of AMI (AMI + NOR) did not change; however, AMI concentration increased, whereas NOR concentration decreased. Conclusions: With this model, we added valuable information on AMI pharmacokinetics during pregnancy (increased AMI concentration, decreased NOR concentration). For clinical practice the treating physician should be aware that despite active moiety serum concentration comparable to before pregnancy, tolerability may be affected due to increased AMI serum concentrations and as consequence increased anticholinergic effects. To keep the risk of therapy discontinuation during pregnancy low, we suggest performing therapeutic drug monitoring, especially to check the AMI serum concentration.en
dc.description.sponsorshipInterdisciplinary Center for Clinical Research (Project number Z-2/CSP-26)en
dc.description.statusPeer revieweden
dc.description.versionAccepted Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationScherf-Clavel, M., Leutritz, A. L., Gehrmann, A., Unterecker, S., Walther, S. and Kittel-Schneider, S. (2025) 'Physiologically based pharmacokinetic modelling predicts altered maternal pharmacokinetics of amitriptyline during pregnancy', British Journal of Clinical Pharmacology. https://doi.org/10.1002/bcp.70084en
dc.identifier.doi10.1002/bcp.70084en
dc.identifier.eissn1365-2125en
dc.identifier.issn0306-5251en
dc.identifier.journaltitleBritish Journal of Clinical Pharmacologyen
dc.identifier.urihttps://hdl.handle.net/10468/17556
dc.language.isoenen
dc.publisherJohn Wiley & Sons, Inc.en
dc.relation.ispartofBritish Journal of Clinical Pharmacologyen
dc.rights© 2025, The British Pharmacological Society. This is the accepted version of the following item: Scherf-Clavel, M., Leutritz, A. L., Gehrmann, A., Unterecker, S., Walther, S. and Kittel-Schneider, S. (2025) 'Physiologically based pharmacokinetic modelling predicts altered maternal pharmacokinetics of amitriptyline during pregnancy', British Journal of Clinical Pharmacology, which has been published in final form at: https://doi.org/10.1002/bcp.70084 . This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.en
dc.subjectAmitriptylineen
dc.subjectPeripartal depressionen
dc.subjectPharmacokineticsen
dc.subjectPBPK-modelingen
dc.titlePhysiologically based pharmacokinetic modelling predicts altered maternal pharmacokinetics of amitriptyline during pregnancyen
dc.typeArticle (peer-reviewed)en
dc.typejournal-articleen
Files
Original bundle
Now showing 1 - 5 of 5
Thumbnail Image
Name:
250411_clean_revised_Original Research Article_oEN.pdf
Size:
408.41 KB
Format:
Adobe Portable Document Format
Description:
Accepted Version
Thumbnail Image
Name:
revised_Electronic Supplementary Material.pdf
Size:
1002.17 KB
Format:
Adobe Portable Document Format
Description:
Supporting Information
Thumbnail Image
Name:
Fig2_PopulationSimulation.png
Size:
1.88 MB
Format:
Portable Network Graphics
Description:
Figure 2
Thumbnail Image
Name:
Fig3_Pregnancy_observedData_2.png
Size:
813.02 KB
Format:
Portable Network Graphics
Description:
Figure 3
Thumbnail Image
Name:
Fig4_Pregnant_Nonpregnant_Comparison.png
Size:
388.46 KB
Format:
Portable Network Graphics
Description:
Figure 4
License bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
license.txt
Size:
2.71 KB
Format:
Item-specific license agreed upon to submission
Description:
Download
Collections
Psychiatry - Journal Articles
APC Microbiome Ireland - Journal Articles