The effect of psychosocial factore(stress) and personal trait on the drug effect

2004 Fiscal Year Final Research Report Summary

• Project/Area Number: 15590468
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Applied pharmacology
• Research Institution: Oita University (2004); 大分医科大学 (2003)
• Principal Investigator: KOTEGAWA Kiniko Oita University, Faculty of Medicine, assistant professor, 医学部, 助手 (20244171)
• Co-Investigator(Kenkyū-buntansha): NAKANO Shigeyuki Oita University, Faculty of Medicine, professor, 医学部, 教授 (10033341) ; KOTEGAWA Tsutomu Oita University, Faculty of Medicine, associate professor, 医学部, 助教授 (20264343) ; SATO Naoko Oita University, Faculty of Medicine, associate professor, 医学部, 助教授 (30359971)
• Project Period (FY): 2003 – 2004
• Keywords: Personality / lorazepam / stress / competition / Maudsley Personality Inventory / Hostility-Guilt Scale / sleep disturbance / TV game

Research Abstract

(1)Distribution of score investigated by Maudsley Personality Inventory and Buss-Durkee Hostility-Guilt Scale in students
Personality of the students of Oita University(male n=64, female n=30) were investigated by using Maudsley Personality Inventory(MPI) and Buss-Durkee Hostility-Guilt(HGS). HGS total score showed a normal distribution with 24.3±7.9(mean±SD).
(2)The effect of personal trait and competition on the pharmacokinetics and the pharmacodynamics of anxiolytics.
Twelve healthy volunteers(Low hostility(L) group(n=6), High hostility(H) group(n=6)) participated in this study with randomized crossover design. The subjects received a single oral dose of lorazepam(LZP) 1mg. Subjects started a TV game 30 minutes before LZP administration. Plasma LZP concentration were determined for 36 hours. Pharmacodynamic effects of LZP were assessed using VAS. and BP/HR. There was no significant effect of TV game on the pharmacokinetics of LZP, while both SBP and HR were significantly increased in t he H group but not in the L group. The results suggested that personal trait is an important factor to be considered when the cardiovascular effect of drug is evaluated in clinical trials.
(3)The effect of experimentally induced sleep disturbance on the pharmacokinetics of lorazepam in healthy volunteers
The effect of sleep disturbance on the pharmacokinetics, especially on the absorption, of LZP was evaluated in humans. Eight healthy male volunteers received a single oral dose of LZP 1 mg before sleep on two occasions in a cross-over design. In either of the two doses, subjects were intermittently exposed to noise for 1.5 hr after oral LZP administration. The exposure to noise significantly prolonged tmax(control vs.noise:2.0 vs.3.0 hr) and significantly decreased AUC of LZP in the absorption phase. The decrement was 54%(95% CI,15 to 75%) and 24%(3 to 40%) for AUC(0-1 hr) and AUC(0-3hr), respectively. No significant changes were observed in other pharmacokinetic parameters. The results of this study suggest that the onset of drug action after oral LZP administration can be altered by sleep disturbance.