Hexobarbitone Disposition at Different Stages of Intensive Care Treatment

Abstract

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.

Pharmacokinetics and Clinical Experience of 20-H Infusions of Methohexitone in Intensive Care Patients With Postoperative Pyrexia

“…The interindividual variation in clearance and V s was considerable in our patients. This parallels the large interindividual variation in the disposition of hexobarbitone found in intensive care patients [7], as a result of altered physiology.…”

“…Induction of hepatic enzymes in conjunction with increased liver blood flow in intensive care patients may increase the clearance of methohexitone to 35 (17) ml min" 1 kg" 1 [8]. Also, the hepatic clearance of hexobarbitone could be enhanced considerably in intensive care patients, in particular in those with infection and fever [7]. Pyrexia may increase the rate of elimination of drugs [7,15].…”

“…Also, the hepatic clearance of hexobarbitone could be enhanced considerably in intensive care patients, in particular in those with infection and fever [7]. Pyrexia may increase the rate of elimination of drugs [7,15]. However, to our knowledge, conclusive evidence for this has been presented for two drugs only, phenytoin [16] and melphalan [17].…”

“…bolus in surgical patients [4,5] and volunteers [5] and with short-term infusions in volunteers [6]; fairly consistent results have been obtained. However, studies with hexobarbitone [7] suggest that pharmacokinetic data from volunteers or "normal" surgical patients may not apply to intensive care patients, in whom physiological functions are altered by factors such as trauma, infection, fever and multi-drug treatment. Thus the clearance of methohexitone was found to be substantially greater in patients with hepatitis than in normal subjects [8].…”

D‐glucaric acid excretion in critical care patients‐comparison with 6 beta‐hydroxycortisol excretion and serum gamma‐glutamyltranspeptidase activity and relation to multiple drug therapy.

“…Figure 3 shows many patients with high values of transaminases, indicating that intensive care treatment may lead to liver damage, for instance by parenteral nutrition (Lindor et al, 1979). Thus, increases in y-GT during the course of intensive care treatment as reported by Rietbrock et al (1979Rietbrock et al ( , 1981, do not necessarily reflect enzyme induction.…”