Soubeyrand J, Comet F, Gillet A, Georges D, Brazier J L
Eur J Clin Pharmacol. 1984;27(3):325-8. doi: 10.1007/BF00542169.
The pharmacokinetics of a new sustained-release preparation of theophylline (Dilatrane à Action Prolongée capsules filled with homogenous microgranules) has been after its studied administration to 7 healthy volunteers at 8 p.m. in order to achieve therapeutic levels at night and in the morning. In separate trials the test dose of 500 or 600 mg was administered for 7 days, once daily at 8 p.m. Plasma theophylline levels were measured by capillary gas chromatography with a mass specific detector after pentylation, using internal standards labelled with stable isotopes (15N-1,3 and 13C-2 theophylline). The new sustained-release preparation showed a monophasic regular absorption phase with very low inter-individual variability. After administration, the plasma level stayed within 80% of the peak levels for 8.5 +/- 1.5 h. There was a good correlation between the dose and the steady state plasma level (r = 0.9587; p less than 0.05). This preparation can be chronically administered once daily day at 8 p.m. in order to achieve a therapeutic level during the night and the morning, and to provide sufficient protection during the nycterohemeral period, with a once dose a day schedule.
为了在夜间和早晨达到治疗水平，对7名健康志愿者于晚上8点给予一种新型茶碱缓释制剂（填充均匀微颗粒的长效氨茶碱胶囊）后，研究了其药代动力学。在单独试验中，给予500或600mg的试验剂量，连续7天，每天晚上8点给药一次。使用稳定同位素标记的内标物（15N-1,3和13C-2茶碱），戊基化后通过带质量特异性检测器的毛细管气相色谱法测定血浆茶碱水平。新型缓释制剂呈现单相规则吸收相，个体间变异性非常低。给药后，血浆水平在峰值水平的80%范围内维持8.5±1.5小时。剂量与稳态血浆水平之间存在良好相关性（r = 0.9587；p＜0.05）。该制剂可以每天晚上8点长期给药一次，以便在夜间和早晨达到治疗水平，并在昼夜期间提供足够的保护，采用每日一次给药方案。
