Schneider G F, Heese G U, Huber H J, Janzen N, Jünger H, Moser C, Stanislaus F
Arzneimittelforschung. 1981;31(9):1489-97.
On the basis of biopharmaceutic-pharmacokinetic and galenic aspects a new sustained-release preparation of theophylline according to the "divided-dose" principle was developed. The technological procedure used allows a reproducible manufacture of a stable product with narrow limits of pharmaceutical quality. The bioavailability of the sustained-release pellets in a dose corresponding to 350 mg active principle is examined in comparison to an aqueous solution or retard-tablet formulation on the marked (containing 260 mg drug/dose), respectively, after single or multiple dose administration to 7 healthy volunteers. The relative bioavailability of the new formulation is about 100%. During chronic application the controlled drug delivery from the sustained-release pellets warrants only slight fluctuations of plasma levels by avoiding peak concentrations. Formulations with a dosage of 200, 350 or 500 mg, respectively, allow adaptation of continuous plasma levels in the therapeutic range between 5--20 micrograms/ml according to the therapeutic necessities of a patient.
基于生物药剂学-药代动力学和药剂学方面的考虑，根据“分剂量”原则开发了一种新型茶碱缓释制剂。所采用的工艺过程能够可重复地生产出质量符合严格药品标准的稳定产品。将相当于350毫克活性成分剂量的缓释微丸的生物利用度，分别与水溶液或标记的缓释片剂配方（每剂量含260毫克药物）进行比较，在对7名健康志愿者进行单次或多次给药后进行测定。新制剂的相对生物利用度约为100%。在长期应用过程中，缓释微丸的控释给药通过避免峰值浓度，保证血浆水平仅有轻微波动。分别为200、350或500毫克剂量的制剂，可根据患者的治疗需要使血浆水平在5-20微克/毫升的治疗范围内持续适应。
