DIDANOSINE (DDL) AND STAVUDINE (D4T) - ABSENCE OF PERIPHERAL NEUROTOXICITY IN RABBITS

Some 20 male New Zealand White rabbits (five/group) were given either didanosine (ddl) or stavudine (d4T) at 750 and 1500 mg/kg body weight/ day by oral intubation for 24 wk. An additional group was given 300 mg /kg body weight/day zidovudine (AZT) as a negative control. After 13 w eeks the high dose of ddl was lowered from 1500 to 1000 mg/kg body wei ght/day following the death of one rabbit and continued inappetence in the dose group. The rabbits were observed daily, plasma drug levels w ere monitored, and electrophysiological measurements of peripheral ner ve conduction were performed during the study. Additionally, body weig ht and food intake were recorded, and clinicopathological parameters w ere evaluated. Sections of selected peripheral nerves, and dorsal and ventral spinal nerve roots were examined by light and transmission ele ctron microscopy. Although peripheral neuropathy has been reported in rabbits with the nucleoside analogue zalcitabine (ddC), based on clini cal observations, electrophysiological measurements, and light and ele ctron microscopy, no evidence of peripheral neurotoxicity was observed in rabbits given either ddl or d4T.