Toxicology and Applied Pharmacology 1992-06-01

Distribution and disposition associated with compartmentation of body fluid in the developing fetus of the rat.

T Nanbo

Index: Toxicol. Appl. Pharmacol. 114(2) , 302-5, (1992)

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Abstract

The relationship between the developmental change of the disposition kinetic character for p-phenylbenzoic acid (PPBA) and compartmentalized fluid of the body was investigated in the rat fetus. [14C]Inulin injected into the umbilical vein attained the steady state distribution at 8 min on Day 17 of gestation and at 10 min on Day 21 of gestation. Inulin space (Vi) on Day 17 of gestation was 0.686 ml/g body wt and decreased to 0.542 ml/g on Day 21 of gestation. [14C]Inulin injected into the fetuses on Days 18 and 21 of gestation remained in the fetal body. Hence a determination method of the apparent volume of distribution (Vd) for PPBA was developed using Vi. Vd on Day 17 of gestation was 0.640 ml/g body wt and decreased to 0.454 ml/g on Day 21 of gestation. Body water based on wet body weight showed no significant change. The analysis of PPBA distribution by the compartmentalization of body fluid suggests that the developmental change of Vd is reflected by that of Vi. The elimination rate (K(el)) from the fetus decreased rapidly in the earlier stages of gestation and slowly in the later stages of gestation. The change of the transplacental clearance (Cl) was mainly reflected by that of K(el) throughout the gestation period. However, the change of Vd partly influenced the change of Cl in the later stage of gestation.