Maternal-fetal electrocardiographic effects and pharmacokinetics after an acute i.v. administration of caffeine to the pregnant rat.
The relationship between fetal exposure and cardiovascular functional effects in the caffeine-treated pregnant rat was investigated. Caffeine (100 mg/kg) was administered intravenously to dams on day 21 of gestation. The transplacental transport of caffeine was studied by obtaining maternal and fetal blood (umbilical vein) samples at designated times after drug administration. Concurrent maternal-fetal electrocardiograms (ECGs) were measured and evaluated for caffeine-induced changes. Maternal and fetal plasma caffeine levels as well as area under the curve values were proportionally related throughout the experiment, indicative of equal exposure to caffeine. The fetal ECG exhibited more extensive changes associated with caffeine than did the dam's, but the effects were not detected in the first 30 min, suggesting a lag period for the action of caffeine on the fetal heart. The frequency of fetal ectopic beats and abnormal T waves were directly related to fetal plasma caffeine levels. Fetal ECG combined with the fetal blood microsampling technique was a practical method of testing for prefunctional effects of caffeine in the rat fetus.
Leal
M
M
Department of Pharmaceutical Sciences, St. John's University, Jamaica, New York.
Barletta
M
M
Carson
S
S
D000818:Animals; D002110:Caffeine / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D004562:Electrocardiography / Q000187:drug effects*; D005260:Female; D005333:Fetus / Q000502:physiology*; D008431:Maternal-Fetal Exchange; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains
D002110:Caffeine