RESUMEN
Preclinical study of therapeutic properties of an innovative drug Doxorubicin-NPh (doxorubicin in the form of ultrafine suspension of phospholipid liposomes) in comparison with free doxorubicin (Doxorubicin-Teva) and protected doxorubicin (Caelyx) was performed on transplanted murine tumor models. All these drugs were efficient in Ca755 breast carcinoma model (tumor growth inhibition ≈100%, increase in lifespan 90.6-114.3%). In P388 lymphocytic leukemia and LLC lung carcinoma, advantages of the protected doxorubicin by the benefit/risk ratio (width of therapeutic interval) were demonstrated: Caelyx>Doxorubicin-NPh>Doxorubicin-Teva. Doxorubicin-NPh and Caelyx exhibited similar therapeutic activity in the LLC model, especially when administered 3 times with 3-day intervals; for Doxorubicin-Teva, the optimal interval between the injections was 7 days.
Asunto(s)
Antibióticos Antineoplásicos/farmacología , Carcinoma Pulmonar de Lewis/tratamiento farmacológico , Doxorrubicina/análogos & derivados , Doxorrubicina/farmacología , Leucemia P388/tratamiento farmacológico , Neoplasias Mamarias Experimentales/tratamiento farmacológico , Aloinjertos , Animales , Antibióticos Antineoplásicos/farmacocinética , Carcinoma Pulmonar de Lewis/patología , Doxorrubicina/farmacocinética , Evaluación Preclínica de Medicamentos , Femenino , Humanos , Leucemia P388/patología , Liposomas/química , Neoplasias Mamarias Experimentales/patología , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos DBA , Fosfolípidos/química , Polietilenglicoles/farmacocinética , Polietilenglicoles/farmacología , Carga Tumoral/efectos de los fármacosRESUMEN
32 patients with chronic calculous cholecystitis were treated by a new preparation. Phosphogliv (on the base of polyunsaturated phospholipids)--5 days before planned surgery and 5 days after. The increase of alanine and asparagine aminotransferases activities and of bilirubin concentration (2-2.5 fold) was observed in all the patients, cirespective of the drug treatment. However, the essential difference between treated and untreated patients was revealed in the course of post-operative period. In the control group asparagine aminotransferase activity and bilirubin level remained high, and alanine aminotransferases activity even more increased. In contrast, both two aminotransferases activities and bilirubin level fell substantially in Phosphogliv group, that may show more active liver regeneration after surgery. Besides, in this group operation did not result even in short-time changes of plasma protein fractions ratios--opposite to control. It may testify on some protective action of Phosphogliv on liver protein-synthesis system. The observed action of new phospholipid preparation Phosphogliv, together with the absence of side effects, allows to recommend it as an adjuvant in the surgery of patients with chronic calculous cholecystitis. Besides, the above results broaden usage field of polyunsaturated phosphatidylcholine as cell membranes repair agent: it appears to be effective not only for liver diseases treatment, but also for soonest overcome of post-surgery liver changes.