Transplacental pharmacokinetics of flecainide in the gravid baboon and fetus.
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 (k(el)) 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 approximately 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.
Dimas
V V
VV
Lillie Frank Abercrombie Section of Pediatric Cardiology, Baylor College of Medicine, Texas Children's Hospital, 6621 Fannin Street, MC 19345-C, Houston, TX 77030, USA. vdimas@bcm.tmc.edu
Dimasc
V V
VV
Taylor
M D
MD
Cunnyngham
C B
CB
Overholt
E D
ED
Bourne
D W A
DW
Stanely
J R
JR
Sheikh
A
A
Wolf
R
R
Valentine
B
B
Ward
K E
KE
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005260:Female; D005312:Fetal Blood / Q000378:metabolism*; D005333:Fetus / Q000378:metabolism*; D005424:Flecainide / Q000008:administration & dosage / Q000493:pharmacokinetics*; D015160:Hydrops Fetalis / Q000517:prevention & control; D007262:Infusions, Intravenous; D008431:Maternal-Fetal Exchange; D010215:Papio; D011247:Pregnancy; D013617:Tachycardia, Supraventricular / Q000517:prevention & control
D000889:Anti-Arrhythmia Agents; D005424:Flecainide