A study on dose control for Tokaimura criticality accident termination.

Verification of the dose control method for Tokaimura criticality accident was performed. Personal dose estimation for accident termination was performed based on measurements of dose rate taken before the work commenced, but the personal dose to workers as a result of the termination work was found to be approximately 50 times higher than the previous estimation. For this report, the doses are reevaluated based on the results of close range measurements from 40 to 100 m, and the results were found to agree with the actual personal doses within the uncertainty of its determination 60-80 %. Therefore, the work can likely be done safely by taking into account factors such as annual dose limits and the guideline dose constraints for works in high-level neutron radiation fields.

Influence of hepatic impairment on the pharmacokinetics and pharmacodynamics of landiolol hydrochloride, an ultra-short-acting beta1-blocker.

OBJECTIVE: To investigate the effects of mild to moderate hepatic impairment on the pharmacokinetics and pharmacodynamics of landiolol hydrochloride, a new ultra-short-acting beta1-adrenergic antagonist. METHODS: Six patients with hepatic impairment and six healthy volunteers were enrolled in the open-label, parallel-group study. Landiolol hydrochloride was given intravenously with a 1-minute loading infusion of 0.06 mg/kg/min, followed by a 60-minute infusion of 0.02 mg/kg/min using an automated infusion pump. Venous blood was drawn just before (predose) and 1, 2, 5, 15, 30 and 61 minutes after beginning the continuous intravenous infusion (during infusion); 2, 5, 10 and 30 minutes and 1, 4 and 8 hours after the end of the infusion (after infusion); and 24 hours after beginning the infusion (next day). Urine samples were collected up to 24 hours after beginning the infusion. Before subjects were discharged, an indocyanine green elimination test, clinical laboratory testing, physical examination and recording of ECGs and vital signs were performed. RESULTS: The geometric mean maximum plasma concentration and area under the concentration-time curve values for the patients with hepatic impairment were 42% and 44% higher, respectively, than those observed for the healthy volunteers, indicating that hepatic impairment affected the disposition of landiolol hydrochloride. There were no significant changes in the elimination half-life of the drug. There were no clinically significant differences between the two groups in terms of reductions in heart rate or blood pressure. CONCLUSION: The pharmacokinetic and pharmacodynamic characteristics of this ultra-short-acting beta1-blocker were maintained even in the patients with hepatic impairment. Although we did not observe any drug-related adverse events in these patients, hypotension or bradycardia should be considered, necessitating continuous monitoring of both heart rate and BP in patients with hepatic impairment who receive landiolol hydrochloride.