Transplacental pharmacokinetics of flecainide in the gravid baboon and fetus

V. V. Dimas, M. D. Taylor, C. B. Cunnyngham, E. D. Overholt, D. W A Bourne, J. R. Stanely, A. Sheikh, R. Wolf, B. Valentine, K. E. Ward

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

The objective of this study was to characterize the transfer of flecainide across the placenta and determine the fetal: maternal ratio of flecainide in the gravid baboon. Flecainide acetate has been especially successful for the treatment of fetal supraventricular tachycardia associated with hydrops fetalis. However, the degree of transplacental transmission remains unknown. In this study, all animals were placed under general anesthesia. Flecainide 2.5 mg/kg was administered intravenously. Percutaneous umbilical blood sampling was performed simultaneously with maternal sampling. Flecainide levels were measured using high-performance liquid chromatography with ultraviolet detection. A total of six gravid baboons were studied at an average gestational age of 132 days. The mean maternal volume of distribution at steady state was 5.1 ± 1.8 L/kg. The mean combined elimination constant (ke1) was 0.79 ± 0.19 hr-1 [95% confidence interval (CI), 0.64-0.93]. There was a linear relationship between maternal and fetal concentrations, with a ratio of fetal-to-maternal serum levels of 0.49 ± 0.05 (95% CI, 0.39-0.59). At steady state, fetal flecainide levels are ∼50% of maternal flecainide levels. Flecainide is rapidly distributed in the mother and fetus following a single intravenous dose with a maternal volume of distribution similar to that reported in normal healthy human adults. Since fetal levels correlate closely with maternal levels, we propose that it is possible to estimate fetal levels by monitoring maternal levels.

Original languageEnglish (US)
Pages (from-to)815-820
Number of pages6
JournalPediatric Cardiology
Volume26
Issue number6
DOIs
StatePublished - Dec 2005

Fingerprint

Flecainide
Papio
Fetus
Pharmacokinetics
Mothers
Cordocentesis
Confidence Intervals
Fetal Monitoring
Hydrops Fetalis
Supraventricular Tachycardia
General Anesthesia
Placenta
Gestational Age
High Pressure Liquid Chromatography

Keywords

  • Fetus
  • Flecainide
  • Supraventricular tachycardia
  • Transplacental pharma kinectics

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Pediatrics, Perinatology, and Child Health

Cite this

Dimas, V. V., Taylor, M. D., Cunnyngham, C. B., Overholt, E. D., Bourne, D. W. A., Stanely, J. R., ... Ward, K. E. (2005). Transplacental pharmacokinetics of flecainide in the gravid baboon and fetus. Pediatric Cardiology, 26(6), 815-820. https://doi.org/10.1007/s00246-005-0974-8

Transplacental pharmacokinetics of flecainide in the gravid baboon and fetus. / Dimas, V. V.; Taylor, M. D.; Cunnyngham, C. B.; Overholt, E. D.; Bourne, D. W A; Stanely, J. R.; Sheikh, A.; Wolf, R.; Valentine, B.; Ward, K. E.

In: Pediatric Cardiology, Vol. 26, No. 6, 12.2005, p. 815-820.

Research output: Contribution to journalArticle

Dimas, VV, Taylor, MD, Cunnyngham, CB, Overholt, ED, Bourne, DWA, Stanely, JR, Sheikh, A, Wolf, R, Valentine, B & Ward, KE 2005, 'Transplacental pharmacokinetics of flecainide in the gravid baboon and fetus', Pediatric Cardiology, vol. 26, no. 6, pp. 815-820. https://doi.org/10.1007/s00246-005-0974-8
Dimas VV, Taylor MD, Cunnyngham CB, Overholt ED, Bourne DWA, Stanely JR et al. Transplacental pharmacokinetics of flecainide in the gravid baboon and fetus. Pediatric Cardiology. 2005 Dec;26(6):815-820. https://doi.org/10.1007/s00246-005-0974-8
Dimas, V. V. ; Taylor, M. D. ; Cunnyngham, C. B. ; Overholt, E. D. ; Bourne, D. W A ; Stanely, J. R. ; Sheikh, A. ; Wolf, R. ; Valentine, B. ; Ward, K. E. / Transplacental pharmacokinetics of flecainide in the gravid baboon and fetus. In: Pediatric Cardiology. 2005 ; Vol. 26, No. 6. pp. 815-820.
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abstract = "The objective of this study was to characterize the transfer of flecainide across the placenta and determine the fetal: maternal ratio of flecainide in the gravid baboon. Flecainide acetate has been especially successful for the treatment of fetal supraventricular tachycardia associated with hydrops fetalis. However, the degree of transplacental transmission remains unknown. In this study, all animals were placed under general anesthesia. Flecainide 2.5 mg/kg was administered intravenously. Percutaneous umbilical blood sampling was performed simultaneously with maternal sampling. Flecainide levels were measured using high-performance liquid chromatography with ultraviolet detection. A total of six gravid baboons were studied at an average gestational age of 132 days. The mean maternal volume of distribution at steady state was 5.1 ± 1.8 L/kg. The mean combined elimination constant (ke1) was 0.79 ± 0.19 hr-1 [95{\%} confidence interval (CI), 0.64-0.93]. There was a linear relationship between maternal and fetal concentrations, with a ratio of fetal-to-maternal serum levels of 0.49 ± 0.05 (95{\%} CI, 0.39-0.59). At steady state, fetal flecainide levels are ∼50{\%} of maternal flecainide levels. Flecainide is rapidly distributed in the mother and fetus following a single intravenous dose with a maternal volume of distribution similar to that reported in normal healthy human adults. Since fetal levels correlate closely with maternal levels, we propose that it is possible to estimate fetal levels by monitoring maternal levels.",
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