Optimizing Therapeutic Drug Monitoring in Pregnant Women: A Critical Literature Review

Abstract

Background: More than 90% of pregnant women take at least one drug during pregnancy. Drug dose adjustments during pregnancy are sometimes necessary due to various pregnancy-induced physiological alterations frequently associated with lower plasma concentrations. However, the clinical relevance or benefits of therapeutic drug monitoring (TDM) in pregnant women have not been specifically studied. Clinical pharmacokinetic studies in pregnant women are incredibly challenging for many reasons. Despite this, regulatory agencies have made efforts to encourage the inclusion of this population in clinical trials to achieve more information on the pharmacotherapy of pregnant women. This review aims to provide support for TDM recommendations and dose adjustments in pregnant women. Methods:The search was conducted after a predetermined strategy on PubMed and Scopus databases using the MeSH term "pregnancy" alongside other terms such as "Pregnancy and dose adjustment," "Pregnancy and therapeutic drug monitoring," "Pregnancy and PBPK," "Pregnancy and pharmacokinetics," and "Pregnancy and physiological changes." Results:The main information on TDM in pregnant women is available for antiepileptics, antipsychotics, antidepressants, antibiotics, antimalarials, and oncologic and immunosuppressive drugs.Conclusions: More data are needed to support informed benefitrisk decision making for the administration of drugs to pregnant women. TDM and/or pharmacokinetic studies could ensure that pregnant women receive an adequate dosage of an active drug. Mechanistic modeling approaches potentially could increase our knowledge about the pharmacotherapy of this special population, and they could be used to better design dosage regimens.

A study on the fine management mode of obstetric pregnancy drugs under the payment of disease diagnosis-related groups (DRG)

“…TDM and/or pharmacokinetic studies can ensure that pregnant women receive adequate doses of the active drug. Mechanistic modeling approaches may increase our understanding of drug therapy in this particular population, and they can be used to better design dose regimens [15].…”

Olanzapine Pharmacokinetics: A Clinical Review of Current Insights and Remaining Questions

“…Olanzapine plasma concentrations in pregnant patients are slightly lower compared to non-pregnant patients which can possibly be attributed to the physiologic changes noted in pregnancy, such as increased clearance and volume of distribution. 65 , 99 In a large cohort of pregnant patients on antipsychotic therapy, maintenance of olanzapine during the first trimester was associated with increased risk of gestational diabetes compared with risperidone, aripiprazole, or ziprasidone. 100 Despite pregnancy-induced changes to olanzapine pharmacokinetics, no specific dosage guidelines have been recommended.…”