-transparent.png){kind=logo}
A physiologically based pharmacokinetic computer model and program have been developed that depict internal disposition of chemicals during pregnancy in the mother and embryo/fetus. The model is based on human physiology but has been extended to simulate laboratory animal data. The model represents the distribution, metabolism, and elimination of two chemicals in both the maternal and embryo/fetal systems; the program handles the two chemicals completely independently or interactively with the two chemicals sharing routes of metabolism and/or elimination. The FORTRAN program computes the concentration of the two chemicals in 26 organs/tissues in the pregnant mother and 15 organs/tissues in the embryo/fetus using a 486DX4 or Pentium PC. Adjustments for embryo/fetal organ and tissue volumes as a function of developmental age are made utilizing the Gompertz growth equation for the developing embryo/fetus and allometric relationships for the developing organs. Various changes in the maternal compartments which could affect the distribution of a xenobiotic during pregnancy are also included in the model. Input files require estimates of binding coefficients, first- and/or second-order metabolism constants, level of interaction between the two chemicals, and dosing information. Different possible routes of administration are included (e.g., i.v., infusion, oral, dermal, and inhalation, as well as repeated doses or exposures). Regression analysis can be conducted on any combination of these various parameters to fit actual data. Output concentration-time curves are available simultaneously from all 82 differential equations. An illustrative example compares observed data with simulations for imipramine and its demethylated metabolite, desipramine, in both the maternal rat and her fetuses. Methyl mercury data for the non-pregnant and pregnant rat also are compared with human data. Based on parameters determined from analysis of rat data, the model is readjusted for human physiology and predicts human maternal and fetal tissue concentrations as a function of time.
R H Luecke, and
W D Wosilait, and
B A Pearce, and
J F Young
December 2002,
Toxicology,
R H Luecke, and
W D Wosilait, and
B A Pearce, and
J F Young
January 1997,
Biopharmaceutics & drug disposition,
R H Luecke, and
W D Wosilait, and
B A Pearce, and
J F Young
January 2008,
Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference,
R H Luecke, and
W D Wosilait, and
B A Pearce, and
J F Young
April 1968,
Journal of theoretical biology,
R H Luecke, and
W D Wosilait, and
B A Pearce, and
J F Young
April 1990,
International journal of bio-medical computing,
R H Luecke, and
W D Wosilait, and
B A Pearce, and
J F Young
January 1982,
International journal of biological research in pregnancy,
R H Luecke, and
W D Wosilait, and
B A Pearce, and
J F Young
January 1989,
Biomedizinische Technik. Biomedical engineering,
R H Luecke, and
W D Wosilait, and
B A Pearce, and
J F Young
January 1991,
Revue francaise de gynecologie et d'obstetrique,
R H Luecke, and
W D Wosilait, and
B A Pearce, and
J F Young
April 1992,
Neurology,
R H Luecke, and
W D Wosilait, and
B A Pearce, and
J F Young
November 2023,
Clinical and translational science,
