Cytochromes P450 Involved in Cyclophosphamide, Paclitaxel and Docetaxel Metabolism in Rats

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Title:Cytochromes P450 Involved in Cyclophosphamide, Paclitaxel and Docetaxel Metabolism in Rats
Creators:
Bořek-Dohalská, Lucie
Gut, Ivan
Souček, Pavel
Roth, Zdeněk
Hodek, Petr
Journal or Publication Title:
Collection of Czechoslovak Chemical Communications, 65, 7, pp. 1183-1190
Uncontrolled Keywords:Enzyme inhibition, Taxanes, Antitumor drugs, Metabolism, Cyclophosphamide, Biotransformations, Docetaxel, Paclitaxel, Cytochrome P450

Abstract

We investigated involvement of cytochromes P450 (CYPs) of rat liver microsomes in metabolism of two anticancer drugs, paclitaxel (PCT) and docetaxel (DTX), by an indirect method. This method is based on the presumption that the compound competitively inhibiting oxidation of the CYP-selective substrate should also be a substrate for the CYP enzyme. The validity of this approach was confirmed using the model drug, cyclophosphamide (CPA). Indeed, CPA competitively inhibited oxidation of substrates specific for CYP2B1 and CYP3A1/2, enzymes previously reported to be capable of metabolizing CPA. Using this method, we identified CYP enzymes participating in PCT and DTX metabolism. The CYP2D1/2/3 and CYP3A1/2 are enzymes oxidizing PCT while CYP3A1/2 and CYP2E1 are responsible for metabolism of DTX. Here, we report a suitable method serving for easy and fast estimation of CYP enzymes involved in drug metabolism.

Title:Cytochromes P450 Involved in Cyclophosphamide, Paclitaxel and Docetaxel Metabolism in Rats
Creators:
Bořek-Dohalská, Lucie
Gut, Ivan
Souček, Pavel
Roth, Zdeněk
Hodek, Petr
Uncontrolled Keywords:Enzyme inhibition, Taxanes, Antitumor drugs, Metabolism, Cyclophosphamide, Biotransformations, Docetaxel, Paclitaxel, Cytochrome P450
Divisions:Life and Chemical Sciences > Institute of Organic Chemistry and Biochemistry > Collection of Czechoslovak Chemical Communications
Journal or Publication Title:Collection of Czechoslovak Chemical Communications
Volume:65
Number:7
Page Range:pp. 1183-1190
ISSN:0010-0765
E-ISSN:1212-6950
Publisher:Institute of Organic Chemistry and Biochemistry
Related URLs:
URLURL Type
http://dx.doi.org/10.1135/cccc20001183UNSPECIFIED
ID Code:1710
Item Type:Article
Deposited On:06 Feb 2009 17:11
Last Modified:06 Feb 2009 16:12

Citation

Bořek-Dohalská, Lucie; Gut, Ivan; Souček, Pavel; Roth, Zdeněk; Hodek, Petr (2000) Cytochromes P450 Involved in Cyclophosphamide, Paclitaxel and Docetaxel Metabolism in Rats. Collection of Czechoslovak Chemical Communications, 65 (7). pp. 1183-1190. ISSN 0010-0765

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