Divided Dose Administration Research Articles

The effect of single and divided dose administration on the efficacy of fenbendazole against adult stages of benzimidazole resistant sheep trichostrongylids

Sheep infected with benzimidazole resistant strains of Haemonchus contortus and Trichostrongylus colubriformis were used to compare the anthelmintic efficacy of fenbendazole given as a single dose or administered in a divided dose regime over five days. Statistical analysis showed no significant difference between the two methods of administration for H contortus. On the other hand, divided dose fenbendazole was significantly less effective than single doses against adult T colubriformis at dose rates of 5 and 7.5 mg/kg. In the case of H contortus a highly significant correlation coefficient between post treatment egg counts and worm counts (r = 0.789) was obtained. This suggests that reduction in faecal egg output following drug treatment would provide a useful field indication of anthelmintic performance of fenbendazole (and possibly related compounds) against benzimidazole resistant strains of this parasite.

Phase I clinical trial of a 3-day divided dose schedule of ifosfamide (NSC 109724)

Twenty patients with unresectable cancer received ifosfamide as a 30 min i.v. infusion daily for 3 days. Dose limiting toxicity was seen in 6 patients and was genitourinary in 4, hematologic in 1, and CNS in 1. Leukopenia was seen in 10 patients, and microscopic hematuria in all except 4 patients. Divided dose administration enabled a larger total dose of drug to be given per treatment course, but did not change the genitourinary nature of the dose limiting toxicity when compared with a high single dose regimen. Total urinary alkylating activity was slightly less following the divided dose administration. For the 3 day divided dose schedule, a daily dose of 2400 mg/m 2 appears to be the maximally tolerated dose.