L01XA01 - Cisplatin |
Not porphyrinogenic |
NP |
Rationale
Non-CYP metabolism. However, side effects such as nausea, anorexia and vomiting may be potentially porphyrinogenic through reduction in caloric intake.
Chemical description
Cisplatin is an inorganic complex that contains a platinum atom surrounded in a plane by 2 chloride atoms and 2 ammonia molecules in the cis position.
Therapeutic characteristics
Cisplatin is a platinum-containing antineoplastic agent used in the treatment of cancer such as ovarial cancer, vescical cancer, testis tumours with metastases, cancers in the head/neck region, and lungcancer. It is administered as an intravenous injection or infusion. Common adverse reactions of cisplatin that can be confused with an acute porphyric attack are vomiting, and nausea. Side effects such as nausea, anorexia and vomiting may be potentially porphyrinogenic through reduction in caloric intake.
Hepatic exposure
Metabolism and pharmakokinetics
Cisplatin has a non-enzymatic metabolism. Excretion is mainly in the urine: up to about 50% of a dose has been reported to be excreted in urine over 5 days, and platinum may be detected in tissue for several months afterwards. The unbound fraction, which is more rapidly cleared, may be actively secreted by the renal tubules. Interactions with CYP metabolism of other drugs not observed. Not listed as CYP-inducer or inhibitor (Rendic 2002). Cisplatin did not exert a significant effect on the PXR-mediated induction of CYP3A4 (Harmsen, 2009). Cisplatin was without inhibitory effect on CYP3A4 (Baumhakel, 2001).
Published experience
Used uneventfully by AIP man in the treatment of testicular cancer (Arbus, 1981).
IPNet drug reports
No.
References
- Scientific articles
- Rendic, S. Summery of information on human CYP enzymes: human P450 metabolism. Drug metabolism reviews 2002; 34(1&2), 83-448. #1025
- Arbus MH. Relationship between porphyria and the use of antineoplastics. Am J Hosp Pharm. 1981;38(5):631. PMID 7282689. #1993
- Baumhäkel M, Kasel D, et al. Screening for inhibitory effects of antineoplastic agents on CYP3A4 in human liver microsomes. Int J Clin Pharmacol Ther. 2001 Dec;39(12):517-28. #2019
- Harmsen S, Meijerman I, et al. Nuclear receptor mediated induction of cytochrome P450 3A4 by anticancer drugs: a key role for the pregnane X receptor. Cancer Chemother Pharmacol. 2009;64(1):35-43. PMID 18839173. #4573
- Drug reference publications
- McEvoy GK, editor. Cisplatin. The AHFS Drug Information 2008. Bethesda, MD: American Society of Health-System Pharmacists; 2009. Electronic version (10.05.10). #2026
- Sweetman SC, editor. Martindale: The complete drug reference. Cisplatin. Pharmaceutical Press 2009. #2027
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