Analysis of factors responsible for adverse drug reactions(ADR) : Studies for rational dosage regimen to avoid ADR

药物不良反应(ADR)因素分析：避免ADR的合理用药方案研究

• 批准号: 15590469
• 负责人: NAKANO Shigeyuki
• 金额: $ 2.11万
• 依托单位: Oita University (2004)大分医科大学 (2003)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15590469/
• 关键词: impaired performance; psychomotor function; loratadine; d-chlorpheniramine; quazepam; itraconazole; fluconazole; adverse drug reaction; クアゼパム; 薬物相互作用; CYP2C9; CYP3A4

(1)The effect of loratadine on psychomotor function measured using a personal computer in healthy Japanese adult subjects : A comparison with d-chlorpheniramine maleate and placebo in a double-blind 4-way crossover studyThe influence of loratadine(10mg or 20mg) on psychomotor function was investigated in healthy adult volunteers using the efficiency of typing figures in a personal computer as an index. The study was performed as a double-blind crossover test using d-chlorpheniramine maleate and placebo as control drugs. The twenty subjects typed figures for 15 minutes after drug administration. Correct typing quantity, total typing quantity and erroneous typing quantity were counted for each subject after each typing job.In a paired comparison among the groups, the numbers of correct figures typed in the chlorpheniramine group was significantly less than that in the placebo group, 10 mg group and 20 mg group of loratadine. No significant difference was observed among the placebo group, … More loratadine 10 mg group and loratadine 20 mg groups. In conclusion, unlike d-chlorpheniramine maleate, loratadine did not influence psychomotor function at all at either the usual dose of 10 mg or the double dose of 20 mg after administration.(2)The effect of itraconazole and fluconazole on the pharmacokinetics and pharmacodynamics of quazepam in healthy volunteersNine healthy volunteers(genotyped as wild type CYP2C9) participated in a randomized double-blind, three-way crossover design. The subjects received single oral dose of quazepam 15mg after 4-day pretreatment of oral itraconazole, fluconazole, or placebo. Plasma concentration of quazepam and its metabolites were determined for 96 hours. Pharmacodynamic effects of quazepam were assessed using continuous number addition test(CNAT) and EEG.Fluconazole caused a significant increase in plasma quazepam concentration, although the EEG change was significantly diminished by fluconazole. This is probably due to the decrease in plasma N-alkyl-2-oxoquazepam(DOQ) concentration. The results suggest that DOQ play a role in the CNS effects of QZP. Less

(1)氯雷他定对日本健康成人用个人电脑测量精神运动功能的影响：与马来酸d-氯苯那敏和安慰剂的双盲4路交叉研究比较。以个人电脑输入数字的效率为指标，研究氯雷他定（10mg或20mg）对健康成人志愿者精神运动功能的影响。本研究采用双盲交叉试验，采用马来酸d-氯苯那敏和安慰剂作为对照药物。20名受试者在给药后15分钟内输入数字。在每个打字作业结束后，统计每个科目的正确打字量、总打字量和错误打字量。在两组之间的配对比较中，氯苯那敏组的数字输入正确率明显低于安慰剂组、氯雷他定10 mg组和20 mg组。安慰剂组、氯雷他定10mg组和氯雷他定20mg组间无显著性差异。总之，与马来酸d-氯苯那敏不同，氯雷他定在常规剂量10mg或给药后双倍剂量20mg时对精神运动功能完全没有影响。(2)伊曲康唑和氟康唑对健康志愿者喹西泮药代动力学和药效学的影响9名健康志愿者（基因型为野生型CYP2C9）采用随机双盲、三向交叉设计。受试者在口服伊曲康唑、氟康唑或安慰剂预处理4天后，给予单次口服喹西泮15mg。测定安定及其代谢物96小时血浆浓度。采用连续数字加法试验（CNAT）和脑电图（EEG）评价安定的药效学效应。氟康唑引起血浆安定浓度显著升高，但氟康唑可显著降低脑电图变化。这可能是由于血浆n -烷基-2-氧喹西泮（DOQ）浓度降低所致。结果表明，DOQ在QZP的中枢神经系统效应中起一定作用。少