B K Park

..The strategic value of fluorine substitution in drug design is discussed in terms of chemical structure and basic concepts in drug metabolism and drug toxicity...

..The long-term aim of such research is to provide test systems for the evaluation of drug safety and patient susceptibility to idiosyncratic drug toxicity...

..This is rapidly detoxified by microsomal epoxide hydrolase, the efficiency of which can be readily determined by measurement of the ratio of the stable metabolites, naphthalene 1,2-dihydrodiol and 1-naphthol...

..AEM was found to be partially converted to two isomeric products, which were identified as the tetrahydrofuran acetate isomer of AEM and 3alpha-hydroxydesoxyartemether...

..This did not affect the kinetic parameters of lymphocyte microsomal epoxide hydrolase. Our results suggest that there is normal HYL1 activity in lymphocytes of hypersensitive patients using cis-stilbene oxide as a substrate...

..In conclusion, the findings of the study expand on potential mechanisms of clozapine-induced cytotoxicity, which may be of relevance to the major forms of toxicity encountered in patients taking this drug...

..O-methyl substitution of DHA favors ring hydroxylation in vivo. However, the principal hydroxylated metabolite, 9alpha-hydroxyAM, is unlikely to possess significant antimalarial activity...

..76 and 0.78 respectively). E binding also correlated with the binding of M (r = 0.79) and Pa (r = 0.81) but not with cytochrome P-450. Binding of Ph and S did not correlate with any of the other measured metabolic parameters...

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..These studies demonstrate the antigenicity of nitroso sulphamethoxazole in vivo and provide evidence for the role of drug metabolism and cell surface haptenation in the induction of a cellular immune response in the rat...

..The purpose of this review is to assess critically the evidence to support the hapten mechanism, and also to consider alternative mechanisms by which drugs cause idiosyncratic toxicity...

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..These results illustrate that danger signals enhance the formation of intracellular SMX-protein adducts in human APC. These findings might be relevant to the increased frequency of drug allergy in certain disease states...

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..Its efficacy is unlikely to be affected by Pgp over-expression in the brain. Furthermore, the interaction of CBZ with drugs that modulate both CYP3A4 and Pgp function such as verapamil is probably due to inhibition of CYP3A4 and not Pgp...

..The inertness of 2,4-DBEE2 to ring-A hydroxylation in male rats conforms with the insignificant debromination of 2,4-dibromoestradiol by hepatic microsomes...

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..A greater understanding of the mechanism(s) of hypersensitivity may identify novel therapeutic strategies and help to combat one of the more severe forms of adverse reactions to drugs...

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..Adrenoceptor stimulation or antagonism can modulate chemical-induced hepatotoxicity. We investigated the role of endogenous catecholamines and alpha(1)-adrenoceptors in the development of paracetamol- induced hepatotoxicity...

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..This indicates that both intracellular and extracellular bioactivation of these two compounds can produce genotoxicity. In contrast, naphthalene and tamoxifen were non-genotoxic...

..These studies characterize drug-specific T cells in CBZ-hypersensitive patients that are phenotypically different from T cells involved in other serious cutaneous adverse drug reactions...

..We therefore conclude that cimetidine may be safely used in patients with RA who are being treated with sulphasalazine...

..The complete data set can be viewed at http://www.ebi.ac.uk/arrayexpress/. The accession number is E-MEXP-82...

..These biomarkers can provide both the means to inform the pharmacologist and chemist with respect to safe drug design, and provide clinicians with valuable tools for patient monitoring...

..We have therefore examined the evidence for the role of reactive metabolites in the three most common drug-induced toxicities: hepatotoxicity, skin reactions and blood dyscrasias...

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..The overall clinical utility of genotyping in preventing ADRs needs to be proven by the use of prospective randomized controlled clinical trials...

..This article will review the advances and challenges of using human pluripotent stem cells for modeling metabolism and toxicity, and offer some perspectives as to where its future may lie...

..0) with UV detection at 285 nm. The method is selective, reproducible and precise with a limit detection of 45 ng/ml and is suitable for the determination of CBZ in murine brain after intra-peritoneal administration...

..The implementation of education, screening and intervention strategies in A&E departments, and employment of key trained personnel, should be considered, to optimize the clinical management of these patients...

..It places GV1001 in the context of other immunotherapeutic approaches targeting telomerase and assesses the chances of the vaccine becoming a future standard of care in the treatment of cancer...

..This is consistent with their mechanisms of toxicity being free radical-mediated damage to redox-sensitive proteins essential for neurite outgrowth, or alteration of a redox-sensitive signalling system which regulates neurite outgrowth...

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