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

(1)氯雷他定对健康日本成年受试者精神运动功能的影响：与马来酸氯苯那敏和安慰剂的双盲四交叉对照研究以个人电脑打字效率为指标，研究氯雷他定(10 mg和20 mg)对健康成年志愿者精神运动功能的影响。该研究采用双盲交叉试验，以马来酸氯苯那敏和安慰剂作为对照药物。20名受试者在服药后15分钟内输入数字。组间配对比较，氯苯那敏组正确数字打字次数明显少于安慰剂组、氯雷他定10 mg组和氯雷他定组20 mg组。在安慰剂组之间没有显著差异，…氯雷他定10 mg组和氯雷他定20 mg组较多。总之，与马来酸氯苯那敏不同，氯雷他定在常规剂量10 mg或双倍剂量20 mg给药后对精神运动功能都没有影响。(2)伊曲康唑和氟康唑对健康志愿者奎西潘药代动力学和药效学的影响9名健康志愿者(基因分型为野生型CYP2C9)参加了随机双盲三交叉设计。受试者在口服伊曲康唑、氟康唑或安慰剂4天后，单次口服奎西潘15 mg。96h后测定奎西潘及其代谢物的血药浓度。用连续数字加法(CNAT)和脑电地形图(EEG)评价奎西潘的药效学效应。氟康唑使奎西潘的血药浓度显著升高，但对脑电的影响明显减弱。这可能是由于血浆N-烷基-2-氧喹西潘(DOQ)浓度下降所致。结果提示，DOQ在清脂丸的中枢神经系统效应中起一定作用。较少

(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