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The urinary excretion of ketamine and its metabolites in the rat [proceedings].

The effect of altering urinary pH of adult male Wistar rats (250-300 g.b.wt.), on the duration of sleeping time following a single injection of ketamine (75 mg/kg i.p.) and the urinary excretion of ketamine and its metabolites was measured. The rats were divided into three groups of ten animals. The first group (A) were given 2% ammonium chloride to drink for 5 days, the second group (B) 2% sodium bicarbonate for 5 days and the third group (C) were given water. After this period the urine from animals in group A had a pH of 5.50 + 0.34 (s.e. mean), group B had a pH of 8.80 + 0.05 and the control animals a pH of 6.90 + 0.23. The rats were injected with ketamine and the sleep- ing time, that is the time between the loss and regain-ing of the righting reflex, was measured. The urine was collected for the two hour period following the injection and assayed for ketamine and its metabolites by a gas-liquid chromatographic method based on that described by Chang & Glazko (1972). There was no difference in the onset time of anaesthesia between the three groups, but the sleeping time was signifi- cantly prolonged (P < 0.001) in the group A animals to 31.1 + 0.9 min compared to the control values of 21.9 + 0.6 minutes. Group B were not significantly different to control with a sleeping time of 24.0 + 1.3 minutes. The rate of excretion of ketamine, metabolite I (the demethylated metabolite) and metabolite II (the subsequent oxidation product) in the urine of control rats (Group C) was 1.00 + 0.13, 3.19 + 0.36 and 0.93