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SYNOPSIS Motor nerve conduction velocity was measured after dosing guinea-pigs with 200-400 ,umol/kg diphenylhydantoin (DPH) daily for three to four days. Conduction velocity fell by a mean value of 13% in animals that achieved plasma DPH levels over 200 ftmol/l. There was no change in velocity with DPH levels below this value.Diphenyihydantoin (DPH) may produce mild peripheral neuropathy in patients who have received the drug for several years (Lovelace and Horwitz, 1968;Eisen et al., 1974;Chokroverty and Sayeed, 1975). Lower limb areflexia, loss of vibration sensation, and occasional slight disturbances of other sensory modalities occur. The motor system is rarely involved and never severely. The incidence of abnormal signs appears to be related to the duration of therapy, rather than to the dose taken. Thus, in 50 unselected patients, Lovelace and Horwitz (1968) found that lower limb reflexes were absent in 18 % of patients treated for more than five years, but in 50 % of those treated for more than 15 years. Chokroverty and Sayeed (1975) Horwitz, 1968;DeCastro et al., 1972;Eisen et al., 1974;Encinoza, 1974;Chokroverty and Sayeed, 1975).In distinction from a mild chronic effect on peripheral nerve function after exposure to DPH for many years, the drug appears to have an acute effect on conduction velocity when given in high doses. When intravenous DPH was given to rabbits Morrell et al. (1958) found some increase in conduction time (Accepted 14 May 1976.) in the posterior tibial nerve, as well as effects on other parameters of nerve excitability. In man, Hopf (1968) found that after treatment for 11 days there was an increase in the range of conduction velocity in the ulnar nerve. There was no effect on maximal velocity, thus suggesting that the smaller and slower conducting fibres were more affected. Birkett-Smith and Krogh (1971) measured motor nerve conduction velocity in a series of patients with high DPH levels in the serum and repeated the estimation about a week later, when the serum level had fallen after reduction in the dose. In patients with initial DPH concentrations above 30 mg/l (120 ,4mol/l) maximal nerve conduction velocity was reduced and when the measurement was repeated the velocity had increased in all. The increase ranged from 0.9 to 14.3 m/s.

A simple, rapid and reproducible reversed-phase HPLC method for clobazam and desmethylclobazam in serum is described that is suitable for both routine use and pharmacokinetic studies.

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