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Metabolism of nitromiphene (CI 628) in the immature female rat: role of gastrointestinal microflora in the biotransformation of a triarylethylene antiestrogen.
Cancer Res. 1986 Dec; 46(12 Pt 1):6255-9.CR

Abstract

Nitromiphene (NIT; CI 628) is a triarylethylene antiestrogen shown to be effective in treatment of experimental breast cancer. We have studied the fate of NIT in the immature female rat, the animal model in which most of the biochemical studies of NIT have been carried out. NIT was eliminated mainly via the feces after i.p. administration, primarily as metabolites. One of these, a diphenylmethane derivative, p-[2-(N-pyrrolidinyl)ethoxy]-p'-methoxybenzophenone (PMB), was also eliminated in urine as such and as its O-demethyl and keto-reduced metabolites. In uterine and liver tissue, unchanged NIT was accompanied by demethyl NIT (CI 628M), PMB, and a diarylacetophenone derivative, p-[2-(N-pyrrolidinyl)ethoxy-p'-hydroxybenzhydryl phenyl ketone (demethyl KET). In vitro studies showed that O-demethyl NIT was produced in the presence of liver enzymes and that PMB and demethyl KET were produced in the presence of intestinal bacteria. These results suggested that PMB and demethyl KET accumulate in uterine and liver tissue due to reabsorption from the intestine after having been produced there from NIT and demethyl NIT, respectively. The effects of antiestrogens and their metabolites may be due in part to interaction with antiestrogen binding sites. Both demethyl KET and PMB had good affinity for such sites. Thus, these enteric bacterial metabolites not only have the ability to accumulate in vivo, but could, together with demethyl NIT, contribute to the antiestrogenic effects observed with NIT.

Authors

No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

3536077

Citation

Ruenitz, P C., and J R. Bagley. "Metabolism of Nitromiphene (CI 628) in the Immature Female Rat: Role of Gastrointestinal Microflora in the Biotransformation of a Triarylethylene Antiestrogen." Cancer Research, vol. 46, no. 12 Pt 1, 1986, pp. 6255-9.
Ruenitz PC, Bagley JR. Metabolism of nitromiphene (CI 628) in the immature female rat: role of gastrointestinal microflora in the biotransformation of a triarylethylene antiestrogen. Cancer Res. 1986;46(12 Pt 1):6255-9.
Ruenitz, P. C., & Bagley, J. R. (1986). Metabolism of nitromiphene (CI 628) in the immature female rat: role of gastrointestinal microflora in the biotransformation of a triarylethylene antiestrogen. Cancer Research, 46(12 Pt 1), 6255-9.
Ruenitz PC, Bagley JR. Metabolism of Nitromiphene (CI 628) in the Immature Female Rat: Role of Gastrointestinal Microflora in the Biotransformation of a Triarylethylene Antiestrogen. Cancer Res. 1986;46(12 Pt 1):6255-9. PubMed PMID: 3536077.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Metabolism of nitromiphene (CI 628) in the immature female rat: role of gastrointestinal microflora in the biotransformation of a triarylethylene antiestrogen. AU - Ruenitz,P C, AU - Bagley,J R, PY - 1986/12/1/pubmed PY - 1986/12/1/medline PY - 1986/12/1/entrez SP - 6255 EP - 9 JF - Cancer research JO - Cancer Res. VL - 46 IS - 12 Pt 1 N2 - Nitromiphene (NIT; CI 628) is a triarylethylene antiestrogen shown to be effective in treatment of experimental breast cancer. We have studied the fate of NIT in the immature female rat, the animal model in which most of the biochemical studies of NIT have been carried out. NIT was eliminated mainly via the feces after i.p. administration, primarily as metabolites. One of these, a diphenylmethane derivative, p-[2-(N-pyrrolidinyl)ethoxy]-p'-methoxybenzophenone (PMB), was also eliminated in urine as such and as its O-demethyl and keto-reduced metabolites. In uterine and liver tissue, unchanged NIT was accompanied by demethyl NIT (CI 628M), PMB, and a diarylacetophenone derivative, p-[2-(N-pyrrolidinyl)ethoxy-p'-hydroxybenzhydryl phenyl ketone (demethyl KET). In vitro studies showed that O-demethyl NIT was produced in the presence of liver enzymes and that PMB and demethyl KET were produced in the presence of intestinal bacteria. These results suggested that PMB and demethyl KET accumulate in uterine and liver tissue due to reabsorption from the intestine after having been produced there from NIT and demethyl NIT, respectively. The effects of antiestrogens and their metabolites may be due in part to interaction with antiestrogen binding sites. Both demethyl KET and PMB had good affinity for such sites. Thus, these enteric bacterial metabolites not only have the ability to accumulate in vivo, but could, together with demethyl NIT, contribute to the antiestrogenic effects observed with NIT. SN - 0008-5472 UR - https://www.unboundmedicine.com/medline/citation/3536077/Metabolism_of_nitromiphene_(CI_628)_in_the_immature_female_rat:_role_of_gastrointestinal_microflora_in_the_biotransformation_of_a_triarylethylene_antiestrogen L2 - http://cancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=3536077 DB - PRIME DP - Unbound Medicine ER -