Therapeutic Drug Monitoring in Pregnancy

Matsui, Doreen

doi:10.1097/ftd.0b013e318261c372

Cited by 26 publications

(24 citation statements)

References 50 publications

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“…4,5,106,113,139,165 Data-driven clinical recommendations for frequency of clinical monitoring and TDM across pregnancy and the postpartum are urgently needed, whereas therapeutic ranges have typically been derived in nonpregnant populations and have not yet been validated in pregnancy. 166 The available data support frequent clinical monitoring of symptoms throughout pregnancy and postpartum; therefore, this is strongly recommended.…”

Section: Discussion and Clinical Recommendationsmentioning

confidence: 99%

Pharmacotherapy for Mood Disorders in Pregnancy

Deligiannidis¹,

Byatt

Freeman³

2014

Journal of Clinical Psychopharmacology

164

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Objective Pharmacotherapy for mood disorders during pregnancy is often complicated by pregnancy-related pharmacokinetic changes and the need for dose adjustments. The objectives of this review are to summarize the evidence for change in perinatal pharmacokinetics of commonly used pharmacotherapies for mood disorders, discuss the implications for clinical and therapeutic drug monitoring (TDM), and make clinical recommendations. Methods The English-language literature indexed on MEDLINE/PubMed was searched for original observational studies (controlled and uncontrolled, prospective and retrospective), case reports, and case series that evaluated or described pharmacokinetic changes or TDM during pregnancy or the postpartum period. Results Pregnancy-associated changes in absorption, distribution, metabolism, and elimination may result in lowered psychotropic drug levels and possible treatment effects, particularly in late pregnancy. Mechanisms include changes in both phase 1 hepatic cytochrome P450 and phase 2 uridine diphosphate glucuronosyltransferase enzyme activities, changes in hepatic and renal blood flow, and glomerular filtration rate. Therapeutic drug monitoring, in combination with clinical monitoring, is indicated for tricyclic antidepressants and mood stabilizers during the perinatal period. Conclusions Substantial pharmacokinetic changes can occur during pregnancy in a number of commonly used antidepressants and mood stabilizers. Dose increases may be indicated for antidepressants including citalopram, clomipramine, imipramine, fluoxetine, fluvoxamine, nortriptyline, paroxetine, and sertraline, especially late in pregnancy. Antenatal dose increases may also be needed for lithium, lamotrigine, and valproic acid because of perinatal changes in metabolism. Close clinical monitoring of perinatal mood disorders and TDM of tricyclic antidepressants and mood stabilizers are recommended.

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Section: Discussion and Clinical Recommendationsmentioning

confidence: 99%

Pharmacotherapy for Mood Disorders in Pregnancy

Deligiannidis¹,

Byatt

Freeman³

2014

Journal of Clinical Psychopharmacology

164

View full text Add to dashboard Cite

show abstract

“…23 Physiologic changes during pregnancy such as increased cardiac output, blood volume, renal perfusion, hepatic blood flow, glomerular filtration, alterations in protein binding and the presence of the fetal-placental unit may lead to pronounced alterations in drug disposition. 33, 34 Race was also considered as a possible factor that influenced the PK with 8 of 11 mothers being African-American (Table I). However, our sample size was not sufficient to answer this question.…”

Section: Discussionmentioning

confidence: 99%

Antenatal Pharmacokinetics and Placental Transfer of N-Acetylcysteine in Chorioamnionitis for Fetal Neuroprotection

Wiest

Chang

Fanning

et al. 2014

The Journal of Pediatrics

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Objective To determine the pharmacokinetics (PK) and placental transfer of intravenous (IV) N-acetylcysteine (NAC) in mothers with a clinical diagnosis of chorioamnionitis and determine the PK of IV NAC in their infants. Study design In this prospective, double blind study IV NAC 100 mg/kg/dose or saline was administered within 4 hours of CA diagnosis to pregnant women ≥24 weeks gestation and then every 6 hours until delivery. Maternal PK and placental transfer were determined with maternal blood and matched maternal and cord venous blood. Neonatal PK estimates were determined from IV NAC (12.5 – 25 mg/kg/dose) administered every 12 hours for 5 doses. Noncompartmental analyses were performed for maternal and neonatal PK estimates. Results Eleven mothers (5 preterm, 6 near-term) and 12 infants (1 set of twins) received NAC. Maternal clearance (CL) of NAC was faster than in non-pregnant adults, with a t1/2 of 1.2 ± 0.2 hours. The NAC cord to maternal ratio was 1.4 ± 0.8 suggesting rapid placental transfer and slower rate of fetal CL. Neonatal PK estimates for near-term compared with preterm infants showed a significantly shorter t1/2 (5.1 vs.7.5 hours, respectively) and higher CL (53.7 vs. 45.0 mL/hr/kg, respectively). Conclusions Maternal CL and placental transfer of NAC was rapid with umbilical cord concentrations frequently exceeding maternal concentrations. NAC administration to mothers with CA achieves predictable NAC plasma concentrations in the fetus, indicating that antenatal neuroprotection may be possible for these newborns at high risk for neuroinflammation.

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“…Although not formally proven by ad hoc studies, it can be reasonably speculated that the same could apply also for other SSRIs, being mainly metabolized not only by CYP2D6 but also by CYP2C19, CYP3A, and CYP1A2 which in turn are encoded by highly polymorphic genes. Accordingly, it could be reasonably hypothesized that monitoring exposure of pregnant women to SSRI through pharmacogenetic approaches or through therapeutic monitoring of plasma SSRI concentrations may favor the early identifications of women at risk which could potentially beneficiate from drug dose adjustments [29]. …”

Section: Discussionmentioning

confidence: 99%

Serotonin Reuptake Inhibitors in Pregnancy: Can Genes Help Us in Predicting Neonatal Adverse Outcome?

Giudici

Pogliani

Cattaneo

et al. 2014

BioMed Research International

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Lots has been written on use of SSRI during pregnancy and possible short and long term negative outcomes on neonates. the literature so far has described a various field of peripartum illness related to SSRI exposure during foetal life, such as increased incidence of low birth weight, respiratory distress, persistent pulmonary hypertension, poor feeding, and neurobehavioural disease. We know that different degrees of outcomes are possible, and not all the newborns exposed to SSRIs during pregnancy definitely will develop a negative outcome. So far, still little is known about the possible etiologic mechanism that could not only explain the adverse neonatal effects but also the degree of clinical involvement and presentation in the early period after birth. Pharmacogenetics and moreover pharmacogenomics, the study of specific genetic variations and their effect on drug response, are not widespread. This review describes possible relationship between SSRIs pharmacogenetics and different neonatal outcomes and summarizes the current pharmacogenetic inquiries in relation to maternal-foetal environment.

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Therapeutic Drug Monitoring in Pregnancy

Cited by 26 publications

References 50 publications

Pharmacotherapy for Mood Disorders in Pregnancy

Pharmacotherapy for Mood Disorders in Pregnancy

Antenatal Pharmacokinetics and Placental Transfer of N-Acetylcysteine in Chorioamnionitis for Fetal Neuroprotection

Serotonin Reuptake Inhibitors in Pregnancy: Can Genes Help Us in Predicting Neonatal Adverse Outcome?

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