Physiologically based pharmacokinetics of methoxyacetic acid: dose-effect considerations in C57BL/6 mice

Teratology
E J O'FlahertyW Scott

Abstract

Methoxyacetic acid (MAA), a weak acid with a pKa of 3.57, was used to test the broad hypothesis that distribution of weak acids in maternal and fetal tissues is determined principally by the pKa of the acid and the pH values of tissue and fluid compartments and to examine tissue dose-teratogenesis relationships, as well as administered dose-teratogenesis relationships. Five related experimental studies were conducted in pregnant C57BL/6CrIBR mice: a conventional dose-response study of developmental toxicity and transplacental pharmacokinetics in mice, a second dose-response study in which reproductive outcomes in litters from individual dams were related to individual pharmacokinetic behavior, a protein-binding experiment, an embryo tissue localization study, and determination of pH in maternal and embryonic compartments after exposure to MAA. MAA was administered intraperitoneally at 9:00 a.m. on day 10 of gestation, at doses ranging from 88 to 164 mg/kg. Localization within the forelimb bud of the embryo, an MAA target site, was determined by computerized image analysis of the distribution of radiolabeled MAA. The kinetic predictions of a physiologically based model incorporating tissue pH values and MAA pKa agreed well with ...Continue Reading

References

Feb 1, 1992·Toxicology and Applied Pharmacology·E J O'FlahertyR P Beliles
Apr 1, 1991·Fundamental and Applied Toxicology : Official Journal of the Society of Toxicology·F B DanielC J Eisenmann
Apr 1, 1988·Toxicology and Applied Pharmacology·R B SleetF Welsch
Aug 1, 1984·Environmental Health Perspectives·B K NelsonP T Goad
Jan 1, 1982·The Journal of Membrane Biology·B Deuticke

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Citations

Nov 1, 1996·Teratology·K K TerryF Welsch
Dec 3, 2014·Reproductive Toxicology·Sieto Bosgra, Joost Westerhout
Apr 23, 2014·Research Quarterly for Exercise and Sport·Amelia Mays Woods, Susan K Lynn

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