Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0000729 (abdominal cramps)
 531 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 9-year-old girl was managed according to the COPRALL 04 protocol for treatment of a relapse of acute lymphoblastic leukemia. Owing to a previous case of disseminated fusariosis, posaconazole was started 5 days before initiation of chemotherapy. Six days after the last dose of vincristine, the child reported symptoms of severe peripheral neuropathy, abdominal cramps, and constipation. After this, she developed fluctuations in her level of consciousness and seizures. After cessation of therapy with posaconazole, a complete resolution of the above occurred within 7 days. This case illustrates the possibility of vincristine toxicity exacerbated by coadministration of posaconazole. As posaconazole is an inhibitor of the isoenzyme CYP3A4, interactions with drugs that are metabolized via this pathway, such as vincristine, can be anticipated. Another possibility is that, like itraconazole, posaconazole may also inhibit P-glycoprotein-mediated vincristine efflux. Although case reports of neurotoxicity owing to possible interaction between itraconazole and vincristine exist in the literature, only 1 case report relating to the possible interaction between posaconazole and vincristine exists. Clinicians should be made aware of this possible drug-drug interaction.
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PMID:Posaconazole-increased vincristine neurotoxicity in a child: a case report. 1934 85

The ingestion of seafood contaminated with the marine biotoxin okadaic acid (OA) can lead to diarrhetic shellfish poisoning with symptoms like nausea, vomiting and abdominal cramps. Both rat and the human hepatic cytochrome P450 monooxygenases (CYP) metabolize OA. However, liver cell toxicity of metabolized OA is mainly unclear. The aim of our study was to detect the cellular effects in HepG2 cells exposed to OA in the presence of recombinant CYP enzymes of both rat and human for the investigation of species differences. The results should be set in correlation with a CYP-specific metabolite pattern. Comparative metabolite profiles of OA after incubation in rat and human recombinant CYP enzymes were established by using LC-MS/MS technique. Results demonstrated that metabolism of OA to oxygenated metabolites correlates with detoxification which was mainly catalyzed by human CYP3A4 and CYP3A5. Detoxification by rat Cyp3a1 was lower compared to human CYP3A enzymes and activation of OA by Cyp3a2 was observed, coincident with minor overall conversion capacity of OA. By contrast human and rat CYP1A2 seem to activate OA into cytotoxic intermediates. In conclusion, different mechanisms of OA metabolism may occur in the liver. At low OA doses, the human liver is likely well protected against cytotoxic OA, but for high shellfish consumers a potential risk cannot be excluded.
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PMID:Differences in metabolism of the marine biotoxin okadaic acid by human and rat cytochrome P450 monooxygenases. 2637 42