Pulse-mediated chemotherapy enhances local control and survival in a spontaneous canine model of primary mucosal melanoma.

Mucosal melanomas account for 1% of all malignant melanomas in humans. Treatment options include surgery, chemotherapy, immunotherapy and radiation therapy; however, local recurrence and distant dissemination are still frequent. We treated locally aggressive spontaneous canine oral melanomas that, because of their advanced stage, were not treatable with conventional strategies. A cohort of 10 dogs with oral melanoma was enrolled over a 4-year period. The dogs received two sessions of local bleomycin, followed by the application of trains of biphasic pulses. The treatment was well tolerated and resulted in an overall response rate of 80% with 50% long-term control. Of interest, only one of the dogs died of metastatic disease, and four of the long-term survivors showed a vitiligo-like discoloration at the site of treatment, potentially suggesting a recruitment of the immune system by the therapy. Further studies are needed to characterize this approach and to determine its suitability for head and neck mucosal melanoma.

Disposition of norfloxacin in broiler chickens and turkeys after different methods of oral administration.

Norfloxacin was administered orally to chickens and turkeys at 15 mg/kg body weight by pulse dosing at 24 h intervals and by continuous dosing at 100 mg/L in drinking water for five days. Blood samples were taken serially. Plasma norfloxacin concentrations were determined by high-performance liquid chromatography. The plasma norfloxacin concentrations increased slowly during continuous dosing and reached the MIC(90) (250 ng/mL) for Gram-negative pathogens by 12 h in chickens and 18 h in turkeys. The steady-state plasma concentration was attained in 36 h and remained at approximately 776.67+/-33.23 ng/mL in chickens and 682.50+/-28.55 ng/mL in turkeys. After pulse dosing, the plasma norfloxacin concentrations increased rapidly and exceeded the MIC(90) at 2 h in both species and remained above MIC(90) for 8 h in chickens and 6 h in turkeys. Pulse dosing provided half the steady-state concentration that was achieved by continuous dosing, 365.32+/-39.31 ng/mL in chickens and 306.03+/-32.26 ng/mL in turkeys, during the dosing interval of 24 h. Data for daily pulse dosing suggested that every administration corresponded to a single, daily repeated bolus administration although pulse dosing produced higher plasma concentrations more readily. Continuous and pulse dosing are both rational for the administration of norfloxacin to flocks of chickens and turkeys. We recommend that treatment be commenced with a pulse oral dose administered over a 4 h period and maintained by continuous oral medication for three to five consecutive days.

Pulse and continuous oral norfloxacin treatment of experimentally induced Escherichia coli infection in broiler chicks and turkey poults.

Experimental colibacillosis was produced in 40 healthy, 7-day-old broiler chickens and turkeys by intratracheal injection of 1 x 10(8) CFU/chick and 1.23 x 10(9) CFU/poult bacteria of an O1:F11 strain of Escherichia coli, respectively. Two days before E. coli challenge all chicks were vaccinated with a live attenuated strain of infectious bronchitis virus (H-52). This model of infection--at least in chicken--proved to be useful for evaluating the efficacy of antimicrobial medication, by recording mortality, body weight gain, pathological alterations and frequency of reisolation of E. coli. Using this model, the efficacy of two different dosing methods of norfloxacin (continuous and pulse dosing) was evaluated. The once-per-day pulse dosing of norfloxacin administered via the drinking water at 15 mg/kg body weight proved to be more efficacious than the continuous dosing method of 100 mg/L for 5 days in chickens, while there were no convincing differences between the two treatment regimens in turkeys. The results confirmed earlier observations on the pharmacokinetic properties of norfloxacin in chicks and turkeys (Laczay et al., 1998).