Abstract
The pharmacokinetics of toloxatone and ethanol were determined in plasma and cerebrospinal fluid of conscious rabbits. According to a cross-over design, rabbits (n = 5) randomly received on three separate occasions either toloxatone (5 mg/kg), ethanol (1 g/kg), or toloxatone and ethanol (5 mg/kg and 1 g/kg, respectively) by intravenous injection. Toloxatone and ethanol concentrations were measured by HPLC with UV detection and GC with flame ionization detection, respectively. Ethanol concentration profiles in plasma were characterized by a rapid decline occurring within the first 30 min after administration followed by a linear (zero-order) phase that persisted for the length of the experiment. The maximum ethanol elimination rate was 0.31+/-0.20 g/h x kg. Toloxatone concentrations in plasma and cerebrospinal fluid were characterized by a multiexponential decay with effective half-lives of 0.39+/-0.06 and 0.56+/-0.07 hr, respectively. Toloxatone passage through the blood brain barrier was rapid and important. Our results also demonstrate that acute ethanol administration had no effect on toloxatone pharmacokinetics and that toloxatone administration had no effect on ethanol pharmacokinetics.
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