An accurate understanding of maternal-fetal pharmacokinetics and pharmacodynamics is pivotal to fetal well being, overall quality of maternity care, and most importantly to avoiding harmful long-term effects on the offspring. Pharmacodynamic parameters of drugs in utero are lacking because such data are difficult to extract during gestation (e.g. ΟΎ600 drugs in the Physician Desk Reference are listed as 'Pregnancy Category C'). We previously showed that combined non-invasive PET and MRI imaging technology allow the measurement of radioisotope distribution in maternal and fetal organs in pregnant non-human primates in vivo. We report here on the use of PET, and MRI for determination of maternal and fetal pharmacodynamic parameters of [ 11 C]cocaine and [ 11 C]nicotine. We measure the maternal and fetal distribution volume ratios (DVR) of striatum (ST) and cerebellum (CB). Preliminary results from five 3 rd trimester pregnant non-human primates demonstrate that [11C]cocaine and/or its metabolites readily cross the placenta and accumulates mainly in fetal liver and brain. Further, time to reach peak C-11 uptake in brain is shorter for the mother than for the fetus. The calculated fetal striatal DVR values were consistently lower than that of maternal values possibly reflecting either reduced receptor binding capacity or different pharmacokinetics factors for the fetus as well as a lower 'recovery coefficient' from the much smaller volume size of fetal ST. Our in vivo model demonstrates significant delivery of cocaine into the fetal brain.
Supported by DOE-OBER.
NBTS 2
Neuroimaging with aMRI/MRSI in prenatally cocaine-exposed children