Development of an Optimum Dosage Regimen for Pentobarbital in Patients with Severe Head Injury

概要

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We attempted to determine the optimum dosage regimen for pentobarbital (PTB) in patients with head injury by using the pharmacokinetic profile obtained by measuring the serum concentration over time after a single intravenous administration of PTB. The optimum loading dose of PTB (0-10 hours) was calculated at 125.2-250.4 mg/hour and the maintenance dose at 24.3-48.6 mg/hour. Therefore, we used loading and maintenance doses of 200 and 50 mg/hour, respectively. Eight of nine patients were intravenously infused for 10 hours at a constant rate with the loading dose of sodium PTB. They were then given the maintenance dose to sustain the optimal serum PTB concentration (15-30 μg/ml) for about 2 days. The serum PTB concentrations gradually decreased despite the constant-rate infusion. In one patient of low body weight, however, the serum PTB concentration was as high as 40-55 μg/ml from 10 to 56 hours after the start of infusion, although the dosage was the same as that of the other patients. The elimination half-life of PTB after cessation of constant-rate infusion was 13.1±2.9 hours, whereas following a single dose it was 39.5±14.9 hours. These results indicate that PTB metabolism is accelerated with long-term infusion and that the dosage regimen we tested is useful for only 2 days in patients weighing 50-75 kg.
日本脳神経外科学会の論文
1987-07-15