Role of cytochrome P450 2C8*3 (CYP2C8*3) in paclitaxel metabolism and paclitaxel-induced neurotoxicity
2015 (English)In: Pharmacogenomics (London), ISSN 1462-2416, E-ISSN 1744-8042, Vol. 16, no 9, 929-937 p.Article in journal (Refereed) Published
Aim: The CYP2C8*3 allele has been suggested as a risk factor for paclitaxel-induced neuropathy but the data hitherto published are conflicting. Materials and methods: In total 435 patients were investigated with respect to maximum neuropathy grade and accumulated paclitaxel dose. The enzymatic properties of CYP2C8.3 variant were analyzed using heterologous mammalian HEK293 cell expression system. Results: No significant association between CYP2C8*3 allele and neuropathy was found, although a trend was observed. The paclitaxel and amodiaquine metabolism by CYP2C8.3 were found similar to CYP2C8.1, whereas CYP2C8.3 was more efficient in the metabolism of rosiglitazone. Conclusion: These results indicate a difference in substrate specificity between CYP2C8.1 and CYP2C8.3; however, the CYP2C8*3 allele has no major impact on paclitaxel metabolism in vitro or of paclitaxel-induced neuropathy in vivo. Original submitted on 6 February 2015; revision submitted on 9 April 2015
Place, publisher, year, edition, pages
Future Medicine , 2015. Vol. 16, no 9, 929-937 p.
amodiaquine; breast cancer; CYP2C8; neuropathy; ovarian cancer; paclitaxel; rosiglitazone
IdentifiersURN: urn:nbn:se:liu:diva-120483DOI: 10.2217/pgs.15.46ISI: 000357864700003PubMedID: 26115084OAI: oai:DiVA.org:liu-120483DiVA: diva2:845509
Funding Agencies|Swedish Research Council; Swedish Cancer Society; County Council in Ostergotland; Spanish Ministry of Economy and Competiveness [SAF2012-35779]; Danish Ministry of Interior Affairs and Health [2006-12103-276]; Danish Research Agency [271-05-0266]2015-08-122015-08-112015-08-12