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K B Bischoff

Publications and source records attributed to K B Bischoff.

15 recordsLinked to original sources
PubMed1984

A physiological model for the pharmacokinetics of methylene chloride in B6C3F1 mice following i.v. administrations.

A physiologic mathematical model was developed to describe the time course of 14C-methylene chloride (14CH2Cl2) distribution and elimination in mice following single i.v. administrations of 10 and 50 mg/kg. A whole-body model was used to simulate 14CH2Cl2 concentrations in blood and tissues, pulmonary clearance of unchanged 14CH2Cl2, and metabolic conversion to 14CO2 and 14CO as monitored by the appearances of these metabolites in expired breath. This diffusion-limited model was identified via a sequential optimization scheme using hybrid models for each compartment. Pulmonary elimination of unchanged 14CH2Cl2 was modeled as a linear process while hepatic metabolism of 14CH2Cl2 to the compounds 14CO2 and 14CO was described by a saturable metabolic rate term. The model adequately described the dose dependence in methylene chloride distribution and metabolism when simulations were compared to experimental data.

Animals↗
PubMed1980

Species similarities in pharmacokinetics.

There are many well documented similarities in the anatomy and physiology of mammalian species. There are also numerous examples in which the equilibrium distribution of foreign chemicals in the body appears to follow principles of thermodynamic partitioning with relatively minor interspecies variations to be expected. Information on metabolic pathways and their kinetic characteristics can be obtained from a variety of in vitro systems. It may be possible to use such information in pharmacokinetic models that incorporate existing knowledge and judgment to predict pharmacokinetics in intact animals including man.

Animals↗
PubMed1977

Wall shear stress distribution in a model canine artery during steady flow.

The wall shear stress pattern was measured in a rigid plastic cast of a canine artery during steady flow by means of an electrochemical technique. The topographic distribution of shear stress is very nonuniform, with regions of high and low shear in close proximity. The steady shear stresses are highest at the leading edge of flow dividers and at the entrance regions to branch vessels. The shapes of the shear stress curves in the celiac branch are primarily a function of the ratio of branch flow to total aortic flow. However, the shapes of the shear stress curves in the adjacent anterior mesenteric branch remain the same for different anterior mesenteric branch flow ratios, although the shear increases with the branch flow ratio. An unstable pattern of flow separation and reattachment is found at the anterior mesenteric flow divider lip and remains localized to that region. A correlation is suggested between sites of high shear stress, extremes in the range of stress, and unstable stress patterns and sites at which atherosclerosis has been shown to develop.

Animals↗
PubMedDate not supplied

Some fundamental considerations of the applications of pharmacokinetics to cancer chemotherapy.

The purpose of this paper is to document the procedures needed to construct pharmacokinetic models based on physiologic, physicochemical, and pharmacologic principles. Extensive descriptions of the basic ideas are provided, along with the corresponding equations. The notions of scaling between various animal species will be described and examples will be given. The important factors determining the choice and number of compartments are based on the properties of the drug and the desired purposes of the pharmacokinetic model. The important concept of flow-limiting conditions with regard to local uptake will be described. The quantitative description of plasma and tissue binding is discussed, along with the notion of effective protein concentrations for the latter. Using these basic ideas, the fundamental mass balances describing the flow, diffusion, and reactions of the drug are presented. An example of the prediction of the pharmacokinetics of a strongly bound drug is used as an illustration of the methods, and this example also indicates the types of useful simplifications that can be made. The special, but important, case of linear binding is next derived, and an example involving the drug methotrexate will illustrate the principles involved. Finally, cytosine arabinoside will be used to indicate methods that can be used for rapidly metabolized drugs. Since existing examples are primarily utilized, this paper brings together a comprehensive collection of the several sets of physiologic data and modeling techniques that have been used for the past several years. It is hoped that this documentation will provide a useful basis for the those wishing to use this approach to pharmacokinetics.

Adipose Tissue↗