Tissue distribution of transdermal toremifene

Lin Soe, Gregory T. Wurz, Juhani U. Mäenpää, Gene B. Hubbard, Timothy B. Cadman, Valerie J. Wiebe, Alain P Theon, Michael W. DeGregorio

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Purpose: Toremifene is an orally administered triphenylethylene derivative with antiestrogenic activity that is primarily used in the treatment of patients with metastatic breast cancer. The purpose of this study was to evaluate the therapeutic advantage of local (transdermal) administration of toremifene in several animal models. Local (subcutaneous and skin) versus systemic concentrations of toremifene were evaluated serially following transdermal application of the drug. With high local concentrations and minimal distribution to other organs via the circulation, topical toremifene may deliver maximal therapeutic effects to local tissue while avoiding the side effects seen with systemic therapy. Methods: Three animal models (nude mice, baboons, and a horse) were used to examine topically administered toremifene for kinetic measurements. Results: In nude mice implanted subcutaneously with MDA-MB-231 human breast tumors, topical toremifene (2.5 mg/day x 5 days) produced greater than 50-fold higher tumor concentrations compared with intraperitoneal (i.p.) administration (1.0 mg/day x 5 days). Systemic distribution in plasma, uterus, and liver was lower following topical than following i.p. administration. In nude mice inoculated subcutaneously with estrogen receptor-positive (ER +) MCF-7 human breast cancer cells, topical toremifene and 4-hydroxytoremifene (4-OH) prevented tumor growth in the presence of estradiol. In four nontumor-bearing baboons that were given transdermal toremifene, relatively high distribution of drug was noted in normal breast tissue and fat; compared with undetectable serum concentrations. Finally, a new topical formulation of toremifene (a gel preparation for human use, Orion-Farmos, Finland) achieved high local tumor toremifene concentrations in a horse melanoma, with minimal systemic distribution. Conclusions: Transdermal toremifene can achieve high local tissue concentrations with minimal systemic distribution.

Original languageEnglish (US)
Pages (from-to)513-520
Number of pages8
JournalCancer Chemotherapy and Pharmacology
Volume39
Issue number6
DOIs
StatePublished - 1997

Fingerprint

Toremifene
Tissue Distribution
Tissue
Tumors
Nude Mice
Papio
Breast Neoplasms
Horses
Animals
Bearings (structural)
Animal Models
Cutaneous Administration
Neoplasms
Therapeutic Uses
Finland
Estrogen Receptors
Pharmaceutical Preparations
Liver
Uterus
Estradiol

Keywords

  • Antiestrogen
  • Breast cancer
  • Toremifene
  • Transdermal

ASJC Scopus subject areas

  • Cancer Research
  • Pharmacology
  • Oncology

Cite this

Soe, L., Wurz, G. T., Mäenpää, J. U., Hubbard, G. B., Cadman, T. B., Wiebe, V. J., ... DeGregorio, M. W. (1997). Tissue distribution of transdermal toremifene. Cancer Chemotherapy and Pharmacology, 39(6), 513-520. https://doi.org/10.1007/s002800050607

Tissue distribution of transdermal toremifene. / Soe, Lin; Wurz, Gregory T.; Mäenpää, Juhani U.; Hubbard, Gene B.; Cadman, Timothy B.; Wiebe, Valerie J.; Theon, Alain P; DeGregorio, Michael W.

In: Cancer Chemotherapy and Pharmacology, Vol. 39, No. 6, 1997, p. 513-520.

Research output: Contribution to journalArticle

Soe, L, Wurz, GT, Mäenpää, JU, Hubbard, GB, Cadman, TB, Wiebe, VJ, Theon, AP & DeGregorio, MW 1997, 'Tissue distribution of transdermal toremifene', Cancer Chemotherapy and Pharmacology, vol. 39, no. 6, pp. 513-520. https://doi.org/10.1007/s002800050607
Soe L, Wurz GT, Mäenpää JU, Hubbard GB, Cadman TB, Wiebe VJ et al. Tissue distribution of transdermal toremifene. Cancer Chemotherapy and Pharmacology. 1997;39(6):513-520. https://doi.org/10.1007/s002800050607
Soe, Lin ; Wurz, Gregory T. ; Mäenpää, Juhani U. ; Hubbard, Gene B. ; Cadman, Timothy B. ; Wiebe, Valerie J. ; Theon, Alain P ; DeGregorio, Michael W. / Tissue distribution of transdermal toremifene. In: Cancer Chemotherapy and Pharmacology. 1997 ; Vol. 39, No. 6. pp. 513-520.
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abstract = "Purpose: Toremifene is an orally administered triphenylethylene derivative with antiestrogenic activity that is primarily used in the treatment of patients with metastatic breast cancer. The purpose of this study was to evaluate the therapeutic advantage of local (transdermal) administration of toremifene in several animal models. Local (subcutaneous and skin) versus systemic concentrations of toremifene were evaluated serially following transdermal application of the drug. With high local concentrations and minimal distribution to other organs via the circulation, topical toremifene may deliver maximal therapeutic effects to local tissue while avoiding the side effects seen with systemic therapy. Methods: Three animal models (nude mice, baboons, and a horse) were used to examine topically administered toremifene for kinetic measurements. Results: In nude mice implanted subcutaneously with MDA-MB-231 human breast tumors, topical toremifene (2.5 mg/day x 5 days) produced greater than 50-fold higher tumor concentrations compared with intraperitoneal (i.p.) administration (1.0 mg/day x 5 days). Systemic distribution in plasma, uterus, and liver was lower following topical than following i.p. administration. In nude mice inoculated subcutaneously with estrogen receptor-positive (ER +) MCF-7 human breast cancer cells, topical toremifene and 4-hydroxytoremifene (4-OH) prevented tumor growth in the presence of estradiol. In four nontumor-bearing baboons that were given transdermal toremifene, relatively high distribution of drug was noted in normal breast tissue and fat; compared with undetectable serum concentrations. Finally, a new topical formulation of toremifene (a gel preparation for human use, Orion-Farmos, Finland) achieved high local tumor toremifene concentrations in a horse melanoma, with minimal systemic distribution. Conclusions: Transdermal toremifene can achieve high local tissue concentrations with minimal systemic distribution.",
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AU - Wiebe, Valerie J.

AU - Theon, Alain P

AU - DeGregorio, Michael W.

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