Determination of Digoxin in the Blood of Pregnant Women, Fetuses and Neonates before and during Anti-arrhythmic Therapy, Using Four Immunochemical Methods

In cases of pregnancies with TTTS a relatively high maternal digoxin level is necessary, especially during early gestational weeks, in order to reach therapeutical levels in the fetal circulation. Too low dosages might be responsible for unfavourable results in digoxin treatment of TTTS. Whether the maturation of placental villi during gestation could be the reason for increasing digoxin gradients requires further investigations.

show abstract

“…Dieser Assay zeichnet sich durch besonders niedrige Kreuzreaktion mit Digoxin ähnlichen Substanzen aus [8].…”

Section: Methodeunclassified

Maternale und fetale Digoxinspiegel bei fetofetalem Transfusionssyndrom (FFTS)*

Pfeiffer¹,

Plath²,

Reinsberg³

et al. 2000

Z Geburtshilfe Neonatol

View full text Add to dashboard Cite

show abstract

Digoxin transfer across the isolated placenta is influenced by maternal and fetal albumin concentrations

Schmolling

Jung²,

Reinsberg³

et al. 1996

Reprod. Fertil. Dev.

View full text Add to dashboard Cite

The aim of this study was to evaluate the influence of different maternal and fetal albumin concentrations on the transplacental transfer and the placental tissue accumulation of digoxin. Digoxin passage across the isolated lobules of 15 human placentae was calculated from repeated fetal and maternal perfusate samples, and placental tissue digoxin concentrations were measured at the end of the experiments. Metildigoxin (Lanitop) was added to the maternal medium at a concentration of 5.70 +/- 0.73 ng mL-1, and maternal and fetal perfusate albumin (BSA) concentrations were kept equal either at a high concentration of 21 g L-1 (Group I; n = 5) or at a low concentration of 3 g L-1 (Group III; n = 5), or differed with a materno-fetal gradient of 21:3 g L-1 (Group II; n = 5). In the experiments with low maternal albumin concentrations (Group III), digoxin concentrations in the maternal circuit decreased to 3.56 ng mL-1, whereas digoxin concentrations in the fetal circuit reached 2.59 ng mL-1 over a 3-h period. With maternal BSA concentrations of 21 g L-1 (Group I and Group II), the decrease in digoxin concentration in the maternal circuit was lower (P < 0.05), and digoxin tissue concentrations at the end of the experiments were smaller (0.45 +/- 0.07 and 0.42 +/- 0.03 v. 0.82 +/- 0.32 ng mg-1 protein, Group I and Group II v. Group III respectively; P < 0.05). Comparing only those lobules with similar high concentrations of maternal protein, fetal BSA concentrations of 21 g L-1 resulted in a greater increase in digoxin concentrations in the fetal circuit (end-feto to initial-maternal digoxin concentrations of 0.44 +/- 0.08 v. 0.37 +/- 0.04 ng mg-1 protein (Group I v. Group II respectively), although this was not significant. The data suggest that maternal and fetal serum albumin concentrations may have an influence on transplacental digoxin transfer, and this should be considered when treating fetuses with cardiac disease transplacentally with glycosides.

show abstract

Transplacental Therapeutic Drug Monitoring in Pregnant Women with Fetal Tachyarrhythmia Using HPLC-MS/MS

Стародубцева

Kindysheva

Potapova

et al. 2023

IJMS

View full text Add to dashboard Cite

Fetal arrhythmia develops in 0.1–5% of pregnancies and may cause fetal heart failure and fetal hydrops, thus increasing fetal, neonatal, and infant mortality. The timely initiation of transplacental antiarrhythmic therapy (ART) promotes the conversion of fetal tachycardia to sinus rhythm and the regression of the concomitant non-immune fetal hydrops. The optimal treatment regimen search for the fetus with tachyarrhythmia is still of high value. Polymorphisms of these genes determines the individual features of the drug pharmacokinetics. The aim of this study was to study the pharmacokinetics of transplacental anti-arrhythmic drugs in the fetal therapy of arrhythmias using HPLC-MS/MS, as well as to assess the effect of the multidrug-resistance gene ABCB1 3435C > T polymorphism on the efficacy and maternal/fetal complications of digoxin treatment. The predisposition to a decrease in the bioavailability of the digoxin in patients with a homozygous variant of the CC polymorphism showed a probable association with the development of ART side effects. A pronounced decrease in heart rate in women with the 3435TT allele of the ABCB1 gene was found. The homozygous TT variant in the fetus showed a probable association with an earlier response to ART and rhythm disruptions on the digoxin dosage reduction. high-performance liquid chromatography with tandem mass spectrometry (HPLC-MS/MS) methods for digoxin and sotalol therapeutic drug monitoring in blood plasma, amniotic fluid, and urine were developed. The digoxin and sotalol concentrations were determined in the plasma blood, urine, and amniotic fluid of 30 pregnant women at four time points (from the beginning of the transplacental antiarrhythmic therapy to delivery) and the plasma cord blood of 30 newborns. A high degree of correlation between the level of digoxin and sotalol in maternal and cord blood was found. The ratio of digoxin and sotalol in cord blood to maternal blood was 0.35 (0.27 and 0.46) and 1.0 (0.97 and 1.07), accordingly. The digoxin concentration in the blood of the fetus at the moment of the first rhythm recovery episode, 0.58 (0.46, 0.8) ng/mL, was below the therapeutic interval. This confirms the almost complete transplacental transfer of sotalol and the significant limitation in the case of digoxin. Previously, ABCB1/P-glycoprotein had been shown to limit fetal exposure to drugs. Further studies (including multicenter ones) to clarify the genetic features of the transplacental pharmacokinetics of antiarrhythmic drugs are needed.

show abstract

Determination of Digoxin in the Blood of Pregnant Women, Fetuses and Neonates before and during Anti-arrhythmic Therapy, Using Four Immunochemical Methods

Cited by 3 publications

References 30 publications

Maternale und fetale Digoxinspiegel bei fetofetalem Transfusionssyndrom (FFTS)*

Maternale und fetale Digoxinspiegel bei fetofetalem Transfusionssyndrom (FFTS)*

Digoxin transfer across the isolated placenta is influenced by maternal and fetal albumin concentrations

Transplacental Therapeutic Drug Monitoring in Pregnant Women with Fetal Tachyarrhythmia Using HPLC-MS/MS

Contact Info

Product

Resources

About