Placental transfer and tissue distribution of thiopental in the pregnant rat.
The pharmacokinetic profile of thiopental was studied in pregnant rats after an iv bolus dose of 15 mg/kg. The unbound concentration-time profile of the drug in maternal plasma, placenta, fetal brain, fetal carcass, and amniotic fluid was described, developing an adequate pharmacokinetic model. Maternal plasma levels of thiopental fell rapidly after injection, distributing into tissues (half-life of distribution phase averaged 3 min). Thiopental crossed the placenta and entered the fetal body (brain included) and amniotic fluid. Peak levels were seen within 10 min of injection and declined in all tissues parallel to maternal plasma (rate constant range 0.012-0.017 min-1). The concentrations of drug in the fetal unit were smaller than in the central compartment and maternal plasma. However, the absolute transfer ratios (calculated using the pharmacokinetic parameters obtained from the model) and the relative exposure ratios (as the ratio of the area under the unbound concentration-time curve in tissue to that in maternal plasma) suggested that fetuses were exposed to a potentially efficacious level of the drug. The model formulated to describe the tissue distribution of thiopental may offer a useful approach for analysis of the kinetic profile of other compounds administered during pregnancy or at delivery in rats and other species.
Celardo
A
A
Laboratory of Clinical Pharmacology, Istituto de Ricerche Farmacologiche Mario Negri, Milan, Italy.
Passerini
F
F
Bonati
M
M
D000653:Amniotic Fluid / Q000378:metabolism; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D005260:Female; D005333:Fetus / Q000378:metabolism; D008954:Models, Biological; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000378:metabolism*; D011359:Proestrus; D051381:Rats; D011919:Rats, Inbred Strains; D013874:Thiopental / Q000493:pharmacokinetics*; D014018:Tissue Distribution
D013874:Thiopental