Positron emission tomography in studies on fetomaternal disposition of opioids.
The noninvasive radiotracer technique, positron emission tomography, has been applied in studies on the transfer of drugs from mother to fetus in Rhesus monkeys. 11C-labelled morphine or heroin was administered intravenously to pregnant monkey and the radioactivities with time were measured in the placenta, fetal liver and maternal blood. The information from the 11C-morphine experiment was supplemented with data from the simultaneous administration of 14C-morphine followed by the analysis of unchanged drug and metabolites in maternal blood and also in one sample from fetal blood. In placenta, 11C-morphine and 11C-heroin rapidly reached high radioactivities already within the first few minutes after administration. The transfer of 11C-morphine-derived radioactivity to the fetus was also rapid, although there was a lag-time in relation to the placental uptake. The elimination rate of the radioactivity was fast from the blood, placenta and the fetal liver and in plasma there was a rapid appearance of conjugated morphine metabolites. The fetal plasma concentration of morphine was twice that in maternal plasma 100 min after injection. The transfer of 11C-heroin-derived radioactivity to the fetus was even faster than was the elimination of radioactivity. The plasma kinetics of morphine in the mother and fetus was simulated in a compartment flow model and simulated concentrations agreed well with measured values.
Hartvig
P
P
Hospital Pharmacy, University of Uppsala, Sweden.
Lindberg
B S
BS
Lilja
A
A
Lundqvist
H
H
Långström
B
B
Rane
A
A
D000818:Animals; D005260:Female; D005333:Fetus / Q000378:metabolism; D003932:Heroin / Q000378:metabolism; D008253:Macaca mulatta; D008431:Maternal-Fetal Exchange; D009020:Morphine / Q000493:pharmacokinetics; D009294:Narcotics / Q000493:pharmacokinetics*; D010920:Placenta / Q000378:metabolism; D011247:Pregnancy; D014055:Tomography, Emission-Computed
D009294:Narcotics; D003932:Heroin; D009020:Morphine