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The relative distribution of gefitinib-related material in nude mice bearing s.c. human tumor xenografts and in an orthotopic rat lung tumor model was investigated following oral administration (50 mg/kg) of [14 C]-gefitinib. Selected tissue samples were monitored for radioactivity by liquid scintillation counting, whereas plasma and tumor extracts were assayed for gefitinib and its major metabolites (M523595 and M537194) by high-performance liquid chromatography with tandem mass spectrometric detection. Tissue distribution was also determined by whole body autoradiography. Gefitinib was extensively distributed into the tissues of tumor-bearing mice and unchanged gefitinib was shown to account for most of the tumor radioactivity. Concentrations of gefitinib in mouse s.c. tumor xenografts were similar to skin concentrations and substantially greater (up to 12-fold based on area under the concentration-time curve) than plasma. Concentrations of gefitinib-related material in an orthotopic rat lung tumor were similar to those in healthy lung tissue and were much higher than corresponding blood levels. Following treatment of breast cancer patients with oral gefitinib (Iressa) 250 mg/d for z z z14 days, gefitinib concentrations (mean, 7.5 A Ag/g, 16.7 A Amol/L) in breast tumor tissue were 42 times higher than plasma, confirming the preferential distribution of gefitinib from blood into tumor tissue in the clinical situation. These gefitinib tumor concentrations are considerably higher than those reportedly required in vitro to achieve complete inhibition of epidermal growth factor receptor autophosphorylation in both epidermal growth factor receptor mutant (0.2 A Amol/L) and wild-type cells (2 A Amol/L). [Mol Cancer Ther 2005;4(4):641 -9]

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Zinc salts (10(-4) and 10(-5) M) inhibited the number of Chlamydia trachomatis inclusions in McCoy, HeLa, and primary human prostate epithelial cell cultures. Addition of zinc salts 1 h before or 24 h after inoculation with C. trachomatis was found to inhibit growth. Both C. trachomatis serotype D and a lymphogranuloma venereum strain were inhibited by the zinc salts. Although the mechanism of inhibition is not known, the continued presence of the zinc appeared necessary for maximal effect. At the concentrations tested, zinc was not directly toxic to the McCoy cells. These results suggest that the levels of zinc in prostatic secretions may be sufficient to preclude the recovery of chlamydia in the diagnostic laboratory or to inhibit chlamydia from infecting the prostate in vivo.