Publication

Pharmacokinetics of clomipramine during pregnancy

Ter Horst, P. G. J., Proost, J. H., Smit, J. P., Vries, M. T., de Jong-van den Berg, L. & Wilffert, B., Dec-2015, In : European Journal of Clinical Pharmacology. 71, 12, p. 1493-1500 8 p.

Research output: Contribution to journalArticleAcademicpeer-review

Copy link to clipboard

Documents

  • Pharmacokinetics of clomipramine during pregnancy

    Final publisher's version, 606 KB, PDF-document

    Request copy

DOI

  • P G J Ter Horst
  • J H Proost
  • J P Smit
  • M T Vries
  • Lolkje de Jong-van den Berg
  • B Wilffert

Clomipramine is one of the drugs for depression during pregnancy; however, pharmacokinetic data of clomipramine and its active metabolite desmethylclomipramine in this vulnerable period are lacking. In this study, we describe clomipramine and desmethylclomipramine concentrations including their ratios during pregnancy. Second, we describe Center for Epidemiologic Studies Depression scale (CES-D) scores during pregnancy.

During 13 pregnancies, every trimester and 3 months after pregnancy, the clomipramine and desmethylclomipramine concentrations were measured with LC-MSMS and the severity of depression was assessed by taking the CES-D score. All concentrations used in our calculations were in fact the ratio between actual plasma concentration (mu g/l) and the actual dose (mg). We compared differences in ratios between trimesters by using the Friedman test.

Studying 12 women and 13 pregnancies, we found no changes in mean clomipramine concentrations, a statistically significant decrease in mean desmethylclomipramine concentrations (p = 0.014) and a significant decrease in the ratio of desmethylclomipramine/clomipramine mean concentrations during pregnancy (p = 0.014) compared to the post-partum period. Sub-therapeutic concentrations of clomipramine and desmethylclomipramine were found in three patients during whole pregnancy.

The mean concentrations of the pharmacologically active metabolite of clomipramine and desmethylclomipramine changes during pregnancy, where a decrease in mean concentrations was found during pregnancy. In case of recurrent disease, we recommend to control clomipramine and its metabolite concentrations, while both are active.

Original languageEnglish
Pages (from-to)1493-1500
Number of pages8
JournalEuropean Journal of Clinical Pharmacology
Volume71
Issue number12
Publication statusPublished - Dec-2015

    Keywords

  • Clomipramine, Desmethylclomipramine, Pregnancy, DEPRESSION, PHARMACOGENETICS, PHARMACOMETRICS, ANTIDEPRESSANTS, GUIDELINES, SYMPTOMS, UPDATE

View graph of relations

ID: 24341044