RESUMO
Rifapentine belongs to the most potent antituberculosis drugs. Nevertheless, there are some limitations for its clinical use because of the low aqueous solubility and side effects. A technological approach to development of rifapentine intravenous formulation based on human serum albumin was described earlier and its efficacy against experimental tuberculosis was estimated. Toxicological evaluation of that water-compatible form of rifapentine revealed its low acute toxicity (LD50 340 mg/kg). Chronic toxicity tests of both the oral substance and the injectable formulation of rifapentine demonstrated similar adverse effects. However, in contrast to the conventional oral formulations, the intravenous formulation of rifapentine had no gastrointestinal toxic effects or cardiotoxicity, thus suggesting its usefulness for clinical application.
Assuntos
Antituberculosos/toxicidade , Coração/efeitos dos fármacos , Rifampina/análogos & derivados , Albumina Sérica Humana/química , Estômago/efeitos dos fármacos , Administração Oral , Fosfatase Alcalina/sangue , Animais , Antituberculosos/química , Bilirrubina/sangue , Feminino , Humanos , Injeções Intravenosas , Rim/efeitos dos fármacos , Dose Letal Mediana , Fígado/efeitos dos fármacos , Masculino , Camundongos , Ratos , Rifampina/química , Rifampina/toxicidade , Albumina Sérica Humana/administração & dosagem , Solubilidade , Sonicação , Baço/efeitos dos fármacos , Testes de Toxicidade Aguda , Testes de Toxicidade CrônicaRESUMO
Hematological toxicity of four combined chemotherapy schemes--TAr, TPAr, EPAr, and IPAr--involving aranose (Ar), cisplatin (P), etoposide (E), irinotecan (I), and topotecan (T) in therapeutic regimes has been studied on healthy mice in comparison to the treatment with Ar in a high therapeutic dose. It is established that Ar alone induces early leucopenia, mostly as a result of lymphocytopenia followed by the absolute and relative neutrophilia; the TAr treatment leads to a moderate neutropenia; whereas the ternary combinations cause a moderate lymphocytopenia. A relatively high hematological toxicity among the ternary combinations was observed for TPAr. The total number of erythrocytes and thrombocytes in the peripheral blood of mice under the action of Ar and all combinations remains on the control level. The inclusion of Ar into the indicated schemes neither modifies the spectrum of hematological toxicity nor increases its level. The observed changes in the peripheral blood were reversible and were not accompanied by any impairment in the state of mice. The obtained results allow the combinations involving P, E, I, T, and Ar to be considered as promising for further investigation.
