RESUMEN
In order to avoid anti-cancer drugs undergoing a first-pass effect and reduce their toxicity, and to solve conventional suppositories defects, we developed an in-situ-gelling and injectable Pluronic-poly(acrylic acid) (Pluronic-PAA) liquid suppository, which could gel fast in the physiological state and had suitable gel strength and bioadhesive force. The liquid suppositories were inserted into the rectum of rabbits without difficulty and leakage, and retained in the rectum for at least 6 h and while releasing the drug. The toxicity and cytotoxic tests indicated that Pluronic and PAA were non-toxic materials and could inhibit colon cancer cells when oxaliplatin was incorporated. C max and AUC0â12h values of oxaliplatin after rectal administration of a oxaliplatin suppository were higher than those for an oxaliplatin solution administered orally. These results suggest that an in-situ-gelling and injectable liquid suppository for humans can be further developed as a more convenient and effective rectal dosage form.
Asunto(s)
Antineoplásicos/administración & dosificación , Neoplasias Colorrectales/tratamiento farmacológico , Geles , Compuestos Organoplatinos/administración & dosificación , Supositorios , Resinas Acrílicas/química , Administración Oral , Administración Rectal , Animales , Antineoplásicos/farmacocinética , Línea Celular , Supervivencia Celular , Liberación de Fármacos , Geles/química , Geles/toxicidad , Humanos , Masculino , Ensayo de Materiales , Compuestos Organoplatinos/farmacocinética , Oxaliplatino , Conejos , Ratas , Recto/efectos de los fármacos , Recto/metabolismo , Soluciones/química , Supositorios/química , Supositorios/toxicidad , Porcinos , ViscosidadRESUMEN
Comparative acute and subacute toxicity of Dentamet gel and Metrovagin suppositories manufactured by ZAO Altaivitaminy was studied with using analogous drugs, i. e. Metrogil Denta, a gel for the gingivae, manufactured by Unique Pharmaceutical Laboratories (India), and Flagil manufactured by Haupt Farma Livron (France) as the reference drugs. It was shown that the drugs induced no changes in the exterior, hair state, body weight and mobility of the experimental animals vs. the control. The pharmacokinetic study of Metrovagin vaginal suppositories vs. the registered analogous drug Flagil showed that Metrovagin was bioequivalent to Flagil. The relative bioavailability of the new drug vs. the control was 103.13%.