Hexobarbitone disposition at different stages of intensive care treatment

The pharmacokinetics of hexobarbitone were investigated in 22 patients in an intensive care unit. The results were compared with those obtained in a healthy group for three time periods: 3rd or 4th day (I), 5-8th days (II) and 13-29th days (III) of treatment. Hexobarbitone 7.32 mg per kg of body weight was administered by i.v. infusion in 60 min. At the end of the infusion, the mean plasma concentration of group I was 71% greater than control group; groups II and III were near to control. In all patients the post-infusion concentration-time course of hexobarbitone could be described by two-compartment kinetics. The biphasic decrease in plasma concentration of hexobarbitone was more rapid in groups II and III, than in either the control group or in group I. At the beginning of treatment patients generally showed an unchanged hexobarbitone half-life, a slightly decreased plasma clearance, a reduction of approximately 50% of the initial distribution volume. (V1) and a reduction of 44% of the distribution volume at steady state. In groups II and III the mean of these values were comparable to control. However, plasma clearance had increased by about 87% in group II compared with control, and after 2-3 weeks (group III) by about 143%. Correspondingly, half-life was reduced by 45% and 58% respectively. The pharmacokinetics were not related to change in liver function. The presence of clinical and bacteriological signs of septicaemia was closely associated with an enhanced hexobarbitone clearance.