Pharmacokinetics of intra-amniotically administered hyperosmolar urea in rhesus monkeys

Three rhesus monkeys in midgestation were injected intra-amniotically with hyperosmolar 14C-urea (58 per cent weight/volume, 2.3 Gm. per kilogram, 25 muc) and the concentration of 14C-urea measured serially for 24 hours in amniotic fluid, maternal serum, and maternal urine. The volume of the amniotic space was measured by isotope dilution of 99mTc-albumin. The experimental values were fitted to a three-compartment mathematical model with the aid of a digital computer program for nonlinear data. The computer-derived concentration versus time curves were in close agreement with the measured values when the flux of urea was primarily from amniotic fluid to fetal water to maternal water with insignificant direct transport between the amniotic fluid and maternal serum. The half-times for distribution of urea into fetus and mother were approximately 30 minutes and 7 hours, respectively. Thus, although the uptake of urea by the fetus from surrounding amniotic fluid is rapid, the further movement of urea from fetus to mother is relatively slow.