Transplacental pharmacokinetics of dideoxyinosine in pigtailed macaques.
To determine whether dideoxyinosine is actively transported across the placenta, four pregnant macques (Macaca nemestrina) near term and their fetuses were infused intravenously in random order with simultaneous doses of dideoxyinosine (42.5 micrograms/min/kg of body weight) and antipyrine (41.7 micrograms/min/kg) for 30 h. The infusions took place after the dams had been chronically catheterized at 128 +/- 0.8 days of gestation. In a third infusion, the dams alone received a higher dosage of dideoxyinosine (425 micrograms/min/kg) and the same dosage of antipyrine (41.7 micrograms/min/kg). Samples of maternal and fetal blood and amniotic fluid were collected at intervals for up to 30 h. The concentrations of dideoxyinosine and antipyrine were determined by high-performance liquid chromatography. The transplacental maternal-fetal drug clearances were compared by the paired Student's t test. The ratio (mean +/- standard deviation) of the steady-state plasma dideoxyinosine concentration in the fetus to that in the dam was 0.49 +/- 0.10 at the low dideoxyinosine infusion rate and 0.51 +/- 0.00 at the high dideoxyinosine infusion rate. The clearance associated with maternal-fetal transfer of the drug, CLdf (0.38 +/- 0.21 ml/min/kg), was not significantly different (P > 0.05) from the clearance associated with fetal-maternal transfer of the drug, CLfd (0.56 +/- 0.27 ml/min/kg). Also, CLdf was not significantly different (P > 0.05) from CLfd when normalized with respect to the corresponding transplacental clearance of antipyrine (0.07 +/- 0.04 CLdf versus 0.09 +/- 0.04 CLfd). ur data indicate that passage of dideoxyinosine across the placenta in pregnant M. nemestrina near term is passive and constant over the dosage range studied.
Department of Pharmaceutics, University of Washington, Seattle 98195.
C M
CM
Pereira
C
C
Nosbisch
H R
HR
Winter
W L
WL
Baughman
J D
JD
Unadkat
D000653:Amniotic Fluid / Q000378:metabolism; D000818:Animals; D000983:Antipyrine / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid; D016049:Didanosine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005260:Female; D005333:Fetus / Q000378:metabolism; D007262:Infusions, Intravenous; D008254:Macaca nemestrina; D008431:Maternal-Fetal Exchange; D008954:Models, Biological; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy
D016049:Didanosine; D000983:Antipyrine