Pharmacokinetic self-potentiation of idarubicin by induction of anthracycline carbonyl reducing enzymes.

Abstract:

:Severe myelosuppression is one of the major adverse effects of Idarubicin (IDA). Especially, after two sequential therapy courses, IDA showed a stronger myelosuppression than after the first course. IDA was metabolized in liver by carbonyl reducing enzymes (CRE) to its 13-OH metabolite, idarubicinol(IDAol),which is more active compared with IDA. RLN-B2, a rat liver cell line, precultured in the presence of IDA showed higher CRE activity compared with non-precultured cells. A crude extract of the enzyme obtained from the livers of F344 rats preadministered IDA 7 days before they were sacrificed showed higher enzymatic activity than that from non-preadministered rats. At 4 h after IDA i.v., the production of IDAol was facilitated in the preadministered group compared with the non-preadministered group. In conclusion, CRE was induced by IDA pretreatment in vitro and vivo, resulting in increased IDAol, which could cause self-potentiation of the myelosuppressive and probably antitumor effects of IDA.

journal_name

Leuk Lymphoma

journal_title

Leukemia & lymphoma

authors

Yamashita T,Fukushima T,Ueda T

doi

10.1080/10428190801947526

subject

Has Abstract

pub_date

2008-04-01 00:00:00

pages

809-14

issue

4

eissn

1042-8194

issn

1029-2403

pii

792011672

journal_volume

49

pub_type

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