Pedersen S, Steffensen G
J Pediatr. 1987 Jun;110(6):953-9. doi: 10.1016/s0022-3476(87)80424-9.
The single- and multiple-dose absorption characteristics of a new sustained-release theophylline preparation, which has been formulated for once per day dosing in adults, were investigated in children aged 8 to 14 years. Four single doses were studied, each dose separated by 1 week. During steady state the preparation was given once daily in the morning for 1 week, and serum theophylline concentration was determined through two dosing intervals (48 hours). The product showed excellent sustained-release characteristics and consistent absorption profiles, which were not affected to any clinically important extent by the intake of various meals. After single doses, only 77% to 91% of the product was absorbed during the first 28 hours after dosing. However, bioavailability was complete both after single doses and during steady state. Eight of 14 children had steady-state fluctuations in serum theophylline levels of less than 90% when given doses once daily. Steady-state day-to-day variations in serum theophylline profiles were small in all patients except one, in whom differences up to 33 mumol/L (6 micrograms/mL) were seen (8 hours after dosing). We conclude that this formulation is completely absorbed at a sufficiently slow and consistent rate to permit acceptable fluctuations in absorption with once daily dosing for many, but not all, patients. However, it should not be used in very young children until bioavailability has been studied in this age group.
一种新的成人每日一次给药的缓释茶碱制剂在8至14岁儿童中进行了单剂量和多剂量吸收特性研究。研究了四个单剂量，每个剂量间隔1周。在稳态期间，该制剂每天早晨给药1周，通过两个给药间隔（48小时）测定血清茶碱浓度。该产品显示出优异的缓释特性和一致的吸收曲线，各种膳食摄入对其吸收曲线无任何临床上显著的影响。单剂量给药后，给药后28小时内仅77%至91%的产品被吸收。然而，单剂量给药后和稳态期间生物利用度均完全。14名儿童中有8名儿童每日一次给药时血清茶碱水平的稳态波动小于90%。除一名患者外，所有患者血清茶碱曲线的稳态每日变化均较小，该患者在给药8小时后差异高达33μmol/L（6μg/mL）。我们得出结论，该制剂以足够缓慢且一致的速率完全吸收，对于许多（但并非所有）患者，每日一次给药时吸收波动在可接受范围内。然而，在该年龄组生物利用度研究完成之前，不应在非常年幼的儿童中使用。
