Impairment of cognitive function associated with hydroxyamylobarbitone accumulation in patients with renal...

1. Sodium amylobarbitone was given by intravenous infusion to six patients with chronic renal insufficiency and to six healthy volunteer subjects. Serum concentrations of amylobarbitone and its major metabolite hydroxyamylobarbitone were measured by a gas chromatograph method.2. The serum concentrations of amylobarbitone were consistently lower in the patient group than in the control group and the concentration half time was shorter (0.10>P>0.05); the 48 h urinary excretion of hydroxyamylobarbitone was reduced (P<0.001) and the serum concentrations of hydroxyamylobarbitone were consistently raised.3. When two patients were given 200 mg of sodium amylobarbitone daily over five consecutive days the serum concentration of hydroxyamylobarbitone rose steadily to a maximum of about 8 mug/ml. The serum concentrations in two healthy control subjects did not exceed 0.5 mug/ml.4. Three parallel tests of cognitive function (Otis matched test forms A, B and C) were given to 16 control patients and to 12 amylobarbitone-treated patients. Significant impairment of performance was observed in test B (P<0.001) at a time when amylobarbitone only could be detected in the patients' serum, and in test C (P<0.001) when amylobarbitone concentrations were very low (0.52+/-0.08 mug/ml+/-SEM) but hydroxyamylobarbitone concentrations were still high (3.30+/-1.23, mug/ml+/-SEM).5. There was a strong (r=-0.71) and significant (P<0.01) negative correlation between the performance in test C and the serum concentration of hydroxyamylobarbitone. It is concluded that hydroxyamylobarbitone has cerebral depressant effects in man.