Disposition kinetics of chemicals with carboxylic, hydroxyl, and amino groups in the near-term fetus of the rat: effect of van der Waals volume on disposition kinetic characteristics.
Disposition kinetics from the near-term fetus of the rat were studied by subcutaneous injection of chemicals into the fetus. These studies were conducted with a series of chemicals having carboxylic, hydroxyl, and amino groups. In homologous groups, the mean residence time (MRT) increased with molecular weight, and clearance (Cl) decreased. These pharmacokinetic parameters in each series were correlated significantly with van der Waals volume (Vw). MRT of the hydroxyl group series was higher and Cl lower when compared with chemicals of other series with similar Vw. The steady-state volume of distribution (Vss) of each series showed no remarkable change with molecular weight. Vss of the hydroxyl group series was the highest, followed in order by those of carboxylic and amino groups. The tissue/plasma concentration ratio of the amino group series was higher than those of other series.
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Tokai Research Laboratories, Daiichi Pure Chemicals Co., Ltd., Ibaraki-ken, Japan.
D000588:Amines / Q000737:chemistry / Q000493:pharmacokinetics*; D000818:Animals; D001798:Blood Proteins / Q000378:metabolism; D002264:Carboxylic Acids / Q000737:chemistry / Q000493:pharmacokinetics*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D005260:Female; D005333:Fetus / Q000378:metabolism*; D006878:Hydroxides / Q000737:chemistry / Q000493:pharmacokinetics*; D008970:Molecular Weight; D011247:Pregnancy; D011485:Protein Binding; D051381:Rats; D017208:Rats, Wistar; D013329:Structure-Activity Relationship
D000588:Amines; D001798:Blood Proteins; D002264:Carboxylic Acids; D006878:Hydroxides