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

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 constantrate 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.