[Amelioration of cisplatin-induced vomiting and anorexia by methylprednisolone]

Amelioration of cisplatin (CDDP)-induced vomiting and anorexia by methylprednisolone (MP) was studied using conscious dogs. The incidence of vomiting was 88.9% and the mean number of emetic episodes was 8.22 +/- 1.25/dog during 5 hours after i.v. administration of 1.5 mg/kg CDDP in 9 dogs. In control dogs, food intake on the day after administration of CDDP was markedly reduced to 60 +/- 22.4 g/day from 461 +/- 23 g. Continuous high-dose infusion of MP (10 mg/kg, 10 min before the start of CDDP infusion and 50 mg/kg/h for 5 h) markedly reduced the incidence (33%) and mean number of vomiting episodes (2.00 +/- 1.51/dog) and also mitigated the reduction of food intake (350 +/- 30.6 g/day). However, continuous low-dose infusion of MP (5 mg/kg, 10 min before CDDP infusion and 16.6 mg/kg/h for 5 h) showed a little effect on CDDP-induced vomiting. Plasma MP levels after the high-dose and the low-dose regimens were 6.20 +/- 0.628 micrograms/ml and 4.66 +/- 1.72 micrograms/ml, respectively, 30 min after CDDP infusion. In both cases, MP levels gradually increased and reached to those more than twice 5 hours after CDDP infusion. Bolus administrations of MP (30 mg/kg, each time) 2 hr and 30 min before CDDP infusion also significantly reduced the mean number of emetic episodes (3.22 +/- 1.33/dog) and mitigated the reduction of food intake (325 +/- 37.3 g/day). No significant changes in catecholamines, prostaglandins, vasopressin, plasma renin activity, Na+, K+, Mg++ and osmolality in peripheral blood were noted after administration of CDDP and/or MP. The results suggest that administration of MP was effective against CDDP-induced vomiting and anorexia in dogs.