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 weeks the high dose of ddl was lowered from 1500 to 1000 mg/kg body weight/day following the death of one rabbit and continued inappetence in the dose group. The rabbits were observed daily, plasma drug levels were monitored, and electrophysiological measurements of peripheral nerve conduction were performed during the study. Additionally, body weight and food intake were recorded, and clinicopathological parameters were evaluated. Sections of selected peripheral nerves, and dorsal and ventral spinal nerve roots were examined by light and transmission electron microscopy. Although peripheral neuropathy has been reported in rabbits with the nucleoside analogue zalcitabine (ddC), based on clinical observations, electrophysiological measurements, and light and electron microscopy, no evidence of peripheral neurotoxicity was observed in rabbits given either ddl of d4T.
Warner
W A
WA
Department of Drug Safety Evaluation, Bristol-Myers Squibb Co., Syracuse, NY 13221-4755, USA.
Bregman
C L
CL
Comereski
C R
CR
Arezzo
J C
JC
Davidson
T J
TJ
Knupp
C A
CA
Kaul
S
S
Durham
S K
SK
Wasserman
A J
AJ
Frantz
J D
JD
D000818:Animals; D000998:Antiviral Agents / Q000633:toxicity*; D016049:Didanosine / Q000097:blood / Q000633:toxicity*; D008297:Male; D008854:Microscopy, Electron; D009431:Neural Conduction / Q000187:drug effects; D009474:Neurons / Q000187:drug effects*; D010525:Peripheral Nerves / Q000187:drug effects* / Q000473:pathology; D011817:Rabbits; D012584:Sciatic Nerve / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D013127:Spinal Nerves / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D018119:Stavudine / Q000097:blood / Q000633:toxicity*; D015215:Zidovudine / Q000097:blood
D000998:Antiviral Agents; D015215:Zidovudine; D018119:Stavudine; D016049:Didanosine