RESUMEN
Using a small database of defined substrates in humans for cytochrome P450 mixed function oxidases, a series of descriptors and classification methods were evaluated with respect to how well they correctly classified substrates. The descriptors ranged from structural keys to topological to electronic. A variety of classification schemes were examined in terms of their ability to point out which descriptors are important for predicting the cytochrome P450 specificity for a substrate. Results illustrate the relative effectiveness of the various kinds of descriptors and classification methods, as well as the value of using as well-defined data set as possible.
Asunto(s)
Citocromos/metabolismo , Evaluación Preclínica de Medicamentos , Especificidad por SustratoRESUMEN
Concerns about cross-allergenicity between sulfonamide antibiotics and nonantibiotic, sulfonamide-containing drugs persist and can complicate patients' drug therapy unnecessarily. No interaction between the human immune system and the sulfonamide functional group has been demonstrated. The immunologic determinant of type I, immediate hypersensitivity responses to sulfonamide antibiotics is the N1 heterocyclic ring. Nonantibiotic sulfonamides do not contain this structural feature. Non-type I hypersensitivity responses to sulfonamide antibiotics are largely attributable to reactive metabolites that may cause either direct cytotoxicity or immunologic response. Formation of these metabolites is a stereospecific process that occurs at the N4 amino nitrogen of the sulfonamide antibiotics, a structure also not found on any nonantibiotic sulfonamide drugs. The stereospecificity of these reactions implies that cross-reactivity with nonantibiotic sulfonamide-containing drugs is highly unlikely; this assertion is supported by recent literature. However, T-cell recognition of unmetabolized, nonhaptenated parent sulfonamide antibiotic appears to occur in a small subset of hypersensitive patients. Several of the severe cutaneous reactions associated with sulfonamide antibiotics are mediated by T cells. It is not known whether T-cell recognition of antibiotic is related to the sulfonamide functional group. Until the mechanism of this recognition is elucidated, cross-reactivity with nonantibiotic sulfonamides appears to remain at least theoretically possible.