ABSTRACT 6-Methylcoumarin (6MC) is a semisynthetic coumarin with important in vitro and in vivo anti-inflammatory activity. In order to continue the pre-clinical characterization of this molecule, in vitro intestinal permeability, plasma profile and tissue distribution after oral administration in rats were studied. The permeability of 6MC was evaluated by the Caco-2 cellular model in both the apical-basal (A-B) and basal-apical (B-A) directions. The pharmacokinetics and biodistribution were evaluated in rats after oral and intraperitoneal administration at doses of 200 mg/kg. Transport experiments with Caco-2 cells showed that 6MC presented high permeability at all concentrations evaluated. This finding suggested that 6MC could be transported across the gut wall by passive diffusion. The plasma concentration-time curve showed that the maximum concentration (Cmax) was 17.13 ± 2.90 µg/mL at maximum time (Tmax) of 30 min for the oral route and Cmax 26.18 ± 2.47 µg/mL at 6.0 min for the intraperitoneal administration, with elimination constant of (Ke ) 0.0070 min-1 and a short life half time of (T1/2 ) lower that 120 min. The distribution study showed that 6MC has high accumulation in the liver, and widespread distribution in all the organs evaluated.

OBJETIVO: La metástasis ósea sigue siendo una de las principales complicaciones del cáncer de mama durante el seguimiento de las pacientes. El objetivo de esta serie fue determinar la prevalencia de las metástasis óseas en pacientes diagnosticadas con adenocarcinoma de mama en nuestra institución, su número y localización, y el tratamiento empleado para su manejo y la sobrevida global de este grupo. MÉTODOS: Se realizó un estudio retrospectivo en pacientes con diagnóstico de adenocarcinoma de mama y metástasis óseas durante diez años, en el lapso comprendido entre 1996 - 2005, mediante la revisión de los expedientes clínicos de 1 610 pacientes femeninas. RESULTADOS: Se encontraron 200 casos con metástasis óseas, diagnosticadas en 90 % mediante gammagrama óseo. Las edades oscilaron entre 41 - 50 años. La enfermedad metastásica ósea fue múltiple en el 55 % de los casos. A todas las pacientes se les aplicó radioterapia. La localización predominante de la metástasis fue en columna vertebral en un 33 %. La sobrevida global fue de un año. CONCLUSIONES: La metástasis ósea en cáncer de mama es una expresión clínica frecuente con el subsiguiente mal pronóstico, corroborado al comparar nuestros resultados con los reportados por la literatura.

OBJECTIVE: Bone metastasis still represents one of the main complications of breast cancer during the follow up of these patients. The objective of the current series was to determine the prevalence of bone metastasis in patients diagnosed of breast adenocarcinoma at our center, the location and number of lesions, treatment selected and the overall patient survival. METHODS: A retrospective study of a group of female patients with a diagnosis of breast adenocarcinoma and bone metastasis was carried out during a ten year period, between the years 1996 and 2005. Medical charts of 1 610 women were analyzed. RESULTS: We found 200 cases with bone metastases, 90 % were diagnosed by bone scans. The ages of these patients ranged between 41 and 50 years. Metastatic bone disease was multiple in 55 % of cases. All the patients received radiotherapy treatment. The main location of the bone lesions was the spine, accounting for 33 % of all cases. Overall survival was one year in this group. CONCLUSIONS: Bone metastasis is a frequent clinical finding in the setting of breast adenocarcinoma. Prognosis is dismal and it is corroborated when we compare our results to those reported in the literature.