Taylor D R, Duffin D, Kinney C D, McDevitt D G
Br J Clin Pharmacol. 1983 Oct;16(4):413-6. doi: 10.1111/j.1365-2125.1983.tb02186.x.
The mechanism of observed temporal variations in plasma theophylline concentrations has been investigated. Eight healthy volunteers were given both oral and intravenous doses of theophylline (5 mg/kg) at 09.00 h and 21.00 h under controlled conditions. Regular plasma concentration measurements were made following each dose in order to determine the diurnal and nocturnal disposition of the drug. Plasma theophylline concentrations at 0.5 h following each oral dose were 6.9 +/- 0.8 micrograms/ml, a.m., and 3.9 +/- 0.6 microgram/ml, p.m. (P less than 0.05). Time to peak concentration was 1.69 +/- 0.28 h, a.m.; 2.13 +/- 0.23 h, p.m. (P less than 0.05). Values for ka were not significantly different, however. Overall bioavailability, volume of distribution and systemic clearances, calculated for the 12 h period after each dose, did not differ significantly between day and night. Diurnal variations in theophylline disposition do not appear to be the result of changes in metabolism or excretion, but may reflect minor differences in absorption.
已对观察到的血浆茶碱浓度随时间变化的机制进行了研究。八名健康志愿者在受控条件下于上午9点和晚上9点分别口服和静脉注射茶碱（5mg/kg）。每次给药后定期测量血浆浓度，以确定药物在白天和夜间的处置情况。每次口服给药后0.5小时的血浆茶碱浓度上午为6.9±0.8μg/ml，下午为3.9±0.6μg/ml（P<0.05）。达峰时间上午为1.69±0.28小时；下午为2.13±0.23小时（P<0.05）。然而，ka值无显著差异。计算每次给药后12小时期间的总体生物利用度、分布容积和全身清除率，白天和夜间之间无显著差异。茶碱处置的昼夜变化似乎不是代谢或排泄变化的结果，而可能反映了吸收方面的微小差异。
