Postrotatory nystagmus during phenytoin treatment

This article reports an investigation into the vestibuloocular reflex (VOR) recorded in rats during acute nontoxic treatment with phenytoin (PHT). In animals adapted to the dark, latency and duration of postrotatory nystagmus (VAN), cumulative trend of slow phases (CTSP), slow-phase velocity, temporal trend of the frequency and amplitude of the nystagmic beats, and mean frequency-amplitude ratio were analyzed. Observations were correlated with plasma and brain levels of the drug. Results showed that an acute nontoxic dose of PHT impairs some parameters of the VAN. At low concentrations (8.24 +/- 2.56) (microgram/ml in plasma and 6.02 +/- 3.24 micrograms/g in brain), only CTSP and slow-phase velocity were remarkably modified in each animal. At higher concentrations but still subthreshold for evoking the appearance of evident signs of drug toxicity (17 +/- 6.13 micrograms/ml in plasma and 11.4 +/- 5.28 micrograms/g in brain), all parameters were modified in each animal. In the same animal, VOR impairment was always linearly correlated to the plasma and brain drug levels. A considerable individual biovariability in the drug response appeared, and an individual subtoxic threshold for each animal was evident. Thus, when results of all experiments were averaged, the statistical significance of the differences of the greater part of the VOR parameters disappeared. However, VOR analysis performed before and after drug administration, i.e., with each subject as its own control, proved to be an excellent diagnostic pointer to the approach of the particular subject's toxic threshold before the appearance of spontaneous nystagmus or postural impairments.