Clearance and disposition of ritodrine in the fluid compartments of the fetal lamb during and after constant rate fetal intravenous infusion.
The disposition of the beta-2 adrenoreceptor agonist, ritodrine, has been examined in the fetal lamb during and after constant rate fetal intravenous infusion (8-24 h). Samples were collected from the fetal femoral artery, umbilical vein, maternal femoral artery, uterine vein, fetal trachea and the amniotic activity for ritodrine quantitation. The amniotic fluid was also analyzed for conjugated metabolites of ritodrine. Ritodrine appears to be cleared across the sheep placenta only to a limited extent (placental clearance 9.2 +/- 2 ml/min/kg; mean +/- S.E.M.). There is, however, significant fetal nonplacental clearance of ritodrine (fetal nonplacental clearance 52.8 +/- 8.0 ml/min/kg). At least part of this clearance appears to be due to fetal drug metabolism, as evidenced by the accumulation of glucuronide conjugates of ritodrine in the amniotic fluid. Ritodrine was also shown to accumulate in the amniotic and fetal tracheal fluids and persist after fetal arterial plasma ritodrine concentrations became undetectable. The accumulation of ritodrine in the tracheal fluid may be of pharmacologic significance, given the well documented, potent effects of beta-2 agonists on fetal lung function and development.
Wright
M R
MR
Division of Pharmaceutics and Biopharmaceutics, Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, Canada.
Rurak
D W
DW
van der Weyde
M P
MP
Taylor
S M
SM
Axelson
J E
JE
D000818:Animals; D001724:Birth Weight; D001825:Body Fluid Compartments / Q000502:physiology*; D005260:Female; D005333:Fetus / Q000378:metabolism*; D007262:Infusions, Intravenous; D010920:Placenta / Q000378:metabolism; D011247:Pregnancy / Q000378:metabolism; D012312:Ritodrine / Q000493:pharmacokinetics*; D012756:Sheep
D012312:Ritodrine