L01BC07 - Azacitidine |
Propably not porphyrinogenic |
PNP |
Rationale
Azacitidine is not an inhibitor, an inducer or a substrate of CYP-enzymes and it is therefore probably not porphyrinogenic. Side effects such as nausea, vomiting, stress, anxiety and insomnia may be potentially porphyrinogenic.
Chemical description
Amino ribofuranosyl triazine. One terminal and three cyclic tertiary amine functions. One furane heterocyclic component.
Therapeutic characteristics
Antineoplastic agent effective via multiple mechanisms.
Common side effects that can be confused with an acute porphyria attack are vomiting, nausea, abdominal pain, diarrhoea, obstipation and musculoskeletal pain. Other common side effects are neutropenic infections (upper respirtory tract infection, urinary infection, sinuitis, pharyngitis, rhinitis, and herpes simplex), stress, anxiety and insomnia.
Hepatic exposure
Significant
Metabolism and pharmakokinetics
In vitro studies have shown that azactidine is not an inhibitor of CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6 and CYP3A4, or an inducer of CYP1A2, CYP2C19 and CYP3A4/5 via activation of CAR or PXR nuclear receptors (Chen 2010, Keating 2012). In vitro studies have also shown that azacitidine is not metabolized by CYP450-enzymes, UDP-glucuronosyltransferases (UGTs), sulfotransferases (SULTs) and glutathione transferases (GSTs) (SPC).
Azacitidine is metabolized by cytidine deaminase (Chabner 1973) and spontaneous hydrolysis (Beisler 1978). 50-85% is excreted in urine, while less than 1% is excreted in faeces. Elimination half-life is 41 ± 8 minutes.
References
- Scientific articles
- Beisler JA. Isolation, characterization, and properties of a labile hydrolysis product of the antitumor nucleoside, 5-azacytidine. J Med Chem. 1978 Feb;21(2):204-8. PMID 74412. #3031
- Chabner BA, Drake JC, Johns DG. Deamination of 5-azacytidine by a human leukemia cell cytidine deaminase. Biochem Pharmacol. 1973 Nov 1;22(21):2763-5. #3032
- Chen Y, Liu L, et al. In vitro assessment of cytochrome P450 inhibition and induction potential of azacitidine. Cancer Chemother Pharmacol. 2010 Apr;65(5):995-1000. PMID 20119716. #4734
- Keating GM. Azacitidine: a review of its use in the management of myelodysplastic syndromes/acute myeloid leukaemia. Drugs. 2012 May 28;72(8):1111-36. #3034
- Summary of Product Characteristics
- Norwegian medicines agency. Summary of Product Characteristics (SPC). (azacitidine). #3035
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