L01AX04 - Dacarbazine |
Propably not porphyrinogenic |
PNP |
Rationale
Not a substrate for CYPs 2C9 or 3A4. Probably not inducer or inhibitor of CYPs 2C9 or 3A4. Side effects as nausea and vomiting may be potentially porphyrinogenic through reduction in caloric intake.
Chemical description
Dacarbazine is a synthetic analog of the naturally occurring purine precursor 5-amino-1H-imidazole-4-carboxamide.
Therapeutic characteristics
Dacarbazine is an antimetabolite antineoplastic agent used to treat malignant melanoma with metastases, or as part of combination therapy in advanced Mb Hodgkin. Administered as an intravenous infusion. Common adverse reactions of dacarbazine that can be confused with an acute porphyric attack are nausea, vomiting, and influenza-like symptoms.
Hepatic exposure
Significant
Metabolism and pharmakokinetics
Metabolized in the liver through hydroxylation and demethylation. Twenty to 50 % of the drug is excreted unchanged by the kidneys. Only 5% binding to plasma proteins. Fifty to 80% of the drug is converted by CYPs 1A1, 1A2 and 2E1 to alkylating metabolites. Not listed as CYP-inducer or CYP-inhibitor. Ineractions with CYP-metabolism of other drugs not observed.
Preclinical data
Cochon et al found dacarbazine to be non-porphyrinogenic in chick embryos (Cochon, A.D. et al, 1997).
IPNet drug reports
No.
References
- Scientific articles
- Rendic, S. Summary of information on human CYP enzymes: human P450 metabolism. Drug metabolism reviews 2002; 34(1&2), 83-448. PMID 11996015. #4559
- Cochón AC, Aldonatti C et al. Evaluation of the porphyrinogenic risk of antineoplastics. J Appl Toxicol 1997;17(3):171-7. PMID 9250538. #3302
- Drug reference publications
- McEvoy GK, editor. Dacarbazine. The AHFS Drug Information 2008. Bethesda, MD: American Society of Health-System Pharmacists; 2009. Electronic version (06.11.2009). #3318
- Sweetman SC, editor. Martindale: The complete drug reference. Dacarbazine. Pharmaceutical Press 2009. #3320
- Other sources
- Swedish National Formulary. FASS. Dacarbazine Medac, Medac. www.fass.se (product leaflet). #3319
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