RESUMO
Prochlorperazine (Compazine; PCPZ) is often used to limit cisplatin (CDDP)-induced emesis. However, recent studies in mice have shown that PCPZ protects against renal injury produced by treatment with various nephrotoxicants (e.g., MethylCCNU, mercuric chloride). Because renal toxicity remains a serious limitation to the effective use of CDDP, we conducted the present study to determine whether PCPZ could also protect against CDDP-induced renal injury. PCPZ treatment was shown to ameliorate CDDP-induced renal lesions in both rats and mice at doses and treatment schedules that were comparable with those used for alleviating chemotherapy-induced emesis. A PCPZ dose of 10 mg/kg x 2 offered complete protection against CDDP-induced increases in blood urea nitrogen (BUN) levels in mice, with significant protection occurring at a PCPZ dose as low as 5 mg/kg. Similarly, PCPZ ameliorated CDDP-induced increases in BUN, glucosouria, and enzymuria in F344 rats. PCPZ treatment did not affect the urinary excretion or renal tissue levels of total platinum or the plasma pharmacokinetics of free platinum. However, it did cause a marked reduction in the concentration of total plasma platinum (free platinum + protein-bound platinum). PCPZ was not found to affect the in vivo antitumor activity of CDDP against P388 leukemia. The present study suggests that PCPZ may be of therapeutic benefit when used with CDDP and provides a rational basis for the selection of antiemetic therapy.
Assuntos
Cisplatino/toxicidade , Rim/efeitos dos fármacos , Proclorperazina/uso terapêutico , Animais , Cisplatino/farmacocinética , Cisplatino/uso terapêutico , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos , Interações Medicamentosas , Rim/metabolismo , Leucemia P388/tratamento farmacológico , Leucemia P388/mortalidade , Masculino , Camundongos , Camundongos Endogâmicos , Ratos , Ratos Endogâmicos F344 , Fatores de TempoRESUMO
A total of 450 brain examinations were performed using computed tomography before and after intravenous infusion of methylglucamine diatrizoate 30%. In 110 cases involving a documented intracranial lesion, the scans were analyzed to determine the degree and usefulness of contrast enhancement. Enhancement was achieved in a wide variety of neoplastic and non-neoplastic lesions and was found to be of considerable help in detection of abnormality as well as in defining tumor morphology.