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核心技术专利：CN118964589B侵权必究

核心技术专利：CN118964589B侵权必究

Jackson S H, Johnston A, Woollard R, Abrams S M, Turner P

Department of Clinical Pharmacology, St Bartholomew's Hospital, London.

Br J Clin Pharmacol. 1988 Jul;26(1):73-7. doi: 10.1111/j.1365-2125.1988.tb03366.x.

Eight volunteers were given seven doses of 200 mg of slow release theophylline at either 11.00 h and 23.00 h (regimen 1) or 17.00 h and 05.00 h (regimen 2). At the time of the sixth dose (60 h) hourly blood sampling was started and continued for 24 h. After at least 1 week volunteers crossed over to the other regimen. 2. Volunteers retired to bed at 23.00 h and arose after the 07.00 h sample during both regimens. 3. During regimen 1 there was a marked rise in mean tmax from 3.3 h after dosing at 11.00 h to 9.3 h after dosing at 23.00 h (P less than 0.001). There was also a fall in AUC(0,12) from 89.9 mg l-1 h after dosing at 11.00 h to 79.0 mg l-1 h after dosing at 23.00 h. There was no difference in mean Cmax values. 4. During regimen 2 these circadian changes were abolished with mean values after both dosing times lying between those observed during regimen 1. 5. A marked delay in absorption occurs at night and cannot be explained by food intake.

八名志愿者分别于上午11点和晚上11点（方案1）或下午5点和凌晨5点（方案2）接受七剂200毫克缓释茶碱。在第六剂给药时（60小时）开始每小时采血，并持续24小时。至少1周后，志愿者交叉采用另一种方案。2. 在两种方案中，志愿者均于晚上11点就寝，并在凌晨7点采样后起床。3. 在方案1中，平均达峰时间（tmax）有显著上升，从上午11点给药后的3.3小时升至晚上11点给药后的9.3小时（P<0.001）。给药后0至12小时的药时曲线下面积（AUC(0,12)）也从上午11点给药后的89.9毫克·升⁻¹·小时降至晚上11点给药后的79.0毫克·升⁻¹·小时。平均峰浓度（Cmax）值无差异。4. 在方案2中，这些昼夜变化被消除，两个给药时间后的平均值介于方案1观察到的值之间。5. 夜间吸收明显延迟，且不能用食物摄入来解释。

Jackson S H, Johnston A, Woollard R, Abrams S M, Turner P

Department of Clinical Pharmacology, St Bartholomew's Hospital, London.

Br J Clin Pharmacol. 1988 Jul;26(1):73-7. doi: 10.1111/j.1365-2125.1988.tb03366.x.

Eight volunteers were given seven doses of 200 mg of slow release theophylline at either 11.00 h and 23.00 h (regimen 1) or 17.00 h and 05.00 h (regimen 2). At the time of the sixth dose (60 h) hourly blood sampling was started and continued for 24 h. After at least 1 week volunteers crossed over to the other regimen. 2. Volunteers retired to bed at 23.00 h and arose after the 07.00 h sample during both regimens. 3. During regimen 1 there was a marked rise in mean tmax from 3.3 h after dosing at 11.00 h to 9.3 h after dosing at 23.00 h (P less than 0.001). There was also a fall in AUC(0,12) from 89.9 mg l-1 h after dosing at 11.00 h to 79.0 mg l-1 h after dosing at 23.00 h. There was no difference in mean Cmax values. 4. During regimen 2 these circadian changes were abolished with mean values after both dosing times lying between those observed during regimen 1. 5. A marked delay in absorption occurs at night and cannot be explained by food intake.

八名志愿者分别于上午11点和晚上11点（方案1）或下午5点和凌晨5点（方案2）接受七剂200毫克缓释茶碱。在第六剂给药时（60小时）开始每小时采血，并持续24小时。至少1周后，志愿者交叉采用另一种方案。2. 在两种方案中，志愿者均于晚上11点就寝，并在凌晨7点采样后起床。3. 在方案1中，平均达峰时间（tmax）有显著上升，从上午11点给药后的3.3小时升至晚上11点给药后的9.3小时（P<0.001）。给药后0至12小时的药时曲线下面积（AUC(0,12)）也从上午11点给药后的89.9毫克·升⁻¹·小时降至晚上11点给药后的79.0毫克·升⁻¹·小时。平均峰浓度（Cmax）值无差异。4. 在方案2中，这些昼夜变化被消除，两个给药时间后的平均值介于方案1观察到的值之间。5. 夜间吸收明显延迟，且不能用食物摄入来解释。