The DOI matches its Crossref record; 15 of the 15 references it cites were found in a registry or an index.
Anticonvulsant hypersensitivity syndrome. In vitro assessment of risk.
Open accessAbstract
Arene oxide metabolites of aromatic anticonvulsants (phenytoin, phenobarbital, and carbamazepine) may be involved in the pathogenesis of hypersensitivity reactions. We investigated 53 patients with clinical sensitivity to anticonvulsants by exposing their lymphocytes in vitro to drug metabolites generated by a murine hepatic microsomal system. The diagnosis of a hypersensitivity reaction was corroborated by in vitro rechallenge for each drug (phenytoin, n = 34; phenobarbital, n = 22; carbamazepine, n = 25) when cytotoxicity (% dead cells) exceeded 3 SD above the mean result for controls. Cross-reactivity among the drugs was noted. 7 out of 10 patients who had received all three anticonvulsants had adverse reactions to each. 40 out of 50 patients tested to all three drugs in vitro were positive to each. Adverse reactions were indistinguishable among anti-convulsants. Skin rash (87%), fever (94%), hepatitis (51%), and hematologic abnormalities (51%) were common clinical features of each drug. 62% of reactions involved more than two organs. Cells from patients' parents exhibited in vitro toxicity that was intermediate between values for controls and patients. In vitro testing can help diagnose hypersensitivity to anticonvulsants. Cells from patients may also be used for prospective individualization of therapy to decrease risk of adverse reaction. Cross-reactivity among the major anticonvulsants is common and should be considered before deciding on alternative therapy.
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Self-citationDrug disposition and drug hypersensitivity
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Cited by
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Stepan, A. F., Walker, D. P., Bauman, J., Price, D. A., Baillie, T. A., Kalgutkar, A. S., & Aleo, M. D. (2011) · Chemical Research in Toxicology · doi:10.1021/tx200168d · Cited by 698
Risk Factors for Idiosyncratic Drug-Induced Liver Injury
Chalasani, N., & Björnsson, E. (2010) · Gastroenterology · doi:10.1053/j.gastro.2010.04.001 · Cited by 347
Genetic susceptibility to adverse drug reactions
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Idiosyncratic Drug Reactions: Current Understanding
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Metadata
- Authors
- Shear, N. H., & Spielberg, S. P.
- Venue
- Journal of Clinical Investigation
- Published
- 1988-12-01
- Volume
- 82
- Issue
- 6
- Pages
- 1826-1832
- ISSN
- 0021-9738 (ISSN-L)
- OpenAlex
- W2079198255
- Cited by
- 687
- References
- 15
- FWCI
- 10.28
- Type
- journal article
- Language
- en
- Open access
- bronze
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