Pharmacokinetic examination of antipyrine passage through the placenta and the small intestine in rats.

Abstract

The placental and small intestinal barriers, though obviously different, show many functional as well as morphological similarities. When the surface area of both barriers in man was recalculated to a unit of body weight, nearly identical values (2.71 and 2.86 m2/kg of body mass, respectively) were obtained. The aims of the present study were (1) to compare mutual permeability of these two barriers to antipyrine (AP), and (2) to describe pharmacokinetics of AP in pregnant and non-pregnant rats. In placental studies AP showed that its rapid transfer through the placenta (k(tr) = 0.046 min(-1)) was governed by the mechanism of passive diffusion. In the closed circuit, FMCR(eq) was 1.085, t(eq) was 112.10 min and k(eq) was 0.020 min(-1). Absorptive studies performed on the rat small intestine indicated an identical mechanism of drug transport. The apparent first-order absorption rate constant of AP was 0.479 min(-1), and Tmax was 8.95 minutes. Differences in AP pharmacokinetics between pregnant and non-pregnant rats were significant during the distribution phase (t(1/2) = 3.78 and 5.87 min, respectively), whereas the elimination phase was unaffected. AP has been demonstrated, as expected, to be an excellent marker for drug transport studies through different body barriers.