The kinetics of amylobarbitone metabolism in healthy men and women

Abstract

1. Sodium amylobarbitone (3.54 mg/kg) was given by intravenous injection to seven healthy men and nine healthy women who were not receiving other drugs. Serum amylobarbitone and urine hydroxyamylobarbitone concentrations were measured by gas-liquid chromatography. There was no significant difference between the groups either in the serum amylobarbitone concentration/time curves or in the urinary excretion of hydroxyamylobarbitone.2. The serum amylobarbitone concentration decayed over 48 h as a double exponential function of time; the first exponential component had a mean half-time of 0.6 h (males 0.56 +/- 0.06 h, females 0.62 +/- 0.08 h, +/- S.E.) and the second exponential component had a mean half time of 21 h (males 22.7 +/- 1.6 h, females 20.0 +/- 1.0 h, +/- S.E.).3. The urinary excretion of hydroxyamylobarbitone over 48 h accounted for 34% of the dose (males 33.8 +/- 3.2%, females 35.2 +/- 3.0%, +/- S.E.). One male and two female subjects excreted hydroxyamylobarbitone partly as a conjugate which was readily hydrolysed in acid.4. An elimination constant (k(el)) derived from the serum concentration/time curve by the application of a two compartment model was approximately proportional to beta (h(-1)), the rate constant of the second exponential component. There was a positive correlation (r=0.78, P<0.001) between beta and the mean rate of urinary excretion of hydroxyamylobarbitone during the 24 to 48 h period.