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• W1977185636 endingPage "498" @default.
• W1977185636 startingPage "489" @default.
• W1977185636 abstract "Tamoxifen is the most used anticancer drug and is approved for chemoprevention. Little is known about the enzyme inducing properties of low-dose regimens and the influence of route of administration. In this study, nude rats received 5 mg/kg/day of tamoxifen orally or a 50 mg continuous-release pellet subcutaneously. The mRNAs for cytochrome P450-enzymes (CYPs), flavin-containing monooxygenase 1 (FMO1) and phase II drug-metabolising enzymes were quantified by real-time RT-PCR. Tamoxifen and metabolite concentrations were measured using HPLC. We observed a significant increase in CYP3A18 and FMO1 mRNA expression levels in the orally treated animals, whereas the increase in CYP3A2 expression did not reach statistical significance (p=0.057). No significant induction of enzyme expression was observed in rats that received subcutaneous (S.c.) treatment. After 33 days the serum levels of 4-hydroxytamoxifen (4OHtam), tamoxifen and N-desmethyltamoxifen (NDtam) in orally treated animals were 1.8+/-0.7, 11.1+/-3.2 and 11.4+/-3.8 ng/ml, respectively. In subcutaneously treated animals, tamoxifen and N-desmethyltamoxifen were detected in tissues, but not in serum. These data demonstrate that in contrast to the subcutaneous administration, low-dose oral tamoxifen induced tamoxifen-metabolising enzymes. Furthermore, the different routes of administration resulted in different serum and tissue levels of tamoxifen and metabolites." @default.
• W1977185636 created "2016-06-24" @default.
• W1977185636 creator A5025942982 @default.
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• W1977185636 creator A5071482852 @default.
• W1977185636 creator A5074988967 @default.
• W1977185636 creator A5086260951 @default.
• W1977185636 date "2005-04-01" @default.
• W1977185636 modified "2023-09-28" @default.
• W1977185636 title "Induction of hepatic drug-metabolising enzymes and tamoxifen metabolite profile in relation to administration route during low-dose treatment in nude rats" @default.
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• W1977185636 doi "https://doi.org/10.1016/j.jsbmb.2004.12.037" @default.
• W1977185636 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/15876414" @default.
• W1977185636 hasPublicationYear "2005" @default.
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