Pharmacokinetic modeling of 4,4'-methylenedianiline released from reused polyurethane dialyzer potting materials
| Autor: | Hoan-My Do Luu, Joseph C. Hutter |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
Physiologically based pharmacokinetic modelling
Gastrointestinal tract Materials science Chromatography 4 4'-Methylenedianiline Biomedical Engineering Absorption (skin) Biomaterials Excretion chemistry.chemical_compound chemistry Pharmacokinetics Distribution (pharmacology) skin and connective tissue diseases Carcinogen Biomedical engineering |
| Zdroj: | Journal of Biomedical Materials Research. 53:276-286 |
| ISSN: | 1097-4636 0021-9304 |
| Popis: | 4, 4'-Methylenedianiline (MDA) is a hydrolysis degradation product that can be released from polyurethanes commonly used in medical device applications. MDA is mutagenic and carcinogenic in animals. In humans, it is hepatotoxic, a known contact and respiratory allergen, and a suspected carcinogen. A physiologically based pharmacokinetic (PBPK) model was developed to estimate the absorption, distribution, metabolism, and excretion of MDA in patients exposed to MDA leached from the potting materials of hemodialyzers. A worst-case reuse situation and a single use case were investigated. The PBPK model included five tissue compartments: liver, kidney, gastrointestinal tract, slowly perfused tissues, and richly perfused tissues. Physiological and chemical parameters of a healthy individual used in the model were obtained from the literature. The model was calibrated using previously published kinetic studies of IV administered doses of (14) C-MDA to rats. The model was validated using independent data published for MDA-exposed workers. The PBPK results indicated that dialysis patients who are exposed to MDA released from dialyzers (new or reused) could accumulate low levels of MDA and metabolites (total MDA) over time. |
| Databáze: | OpenAIRE |
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