Jonkman J H, Grasmeijer G, Holland A
Pharma Bio-Research Int'l.b.v., Department of Biopharmaceutics and Clinical Pharmacology, Assen, The Netherlands.
Int J Clin Pharmacol Ther Toxicol. 1987 Nov;25(11):633-7.
In a two-way single dose crossover experiment in 12 healthy young adults the influence of food (breakfast) on the absorption profiles and bioavailability of theophylline was investigated when the drug was given as Dilatrane A. P. 400 mg capsules (Fisons), a once-a-day sustained-release preparation. The capsule was taken at 8:00 a. m. either after a 10-h fast or immediately after a standard breakfast, yielding 1990 kJ. Theophylline in plasma was measured by high pressure liquid chromatography over a period of 48 h. The food caused a slight but not significant (p greater than 0.05, Student's paired t-test) increase in the time to peak (tmax, 9.4 +/- 1.3 h vs. 8.4 +/- 1.7 h, mean +/- SD) and in the area under the curve (AUC0-48, 114.3 +/- 41.7 mg.l-1.h vs. 105.3 +/- 36.5 mg.l-1.h), the relative bioavailability being 108.9 +/- 12.4%, as compared with ingestion of the capsule in fasted state. Maximum theophylline concentrations in plasma were slightly but significantly higher (cmax, 6.50 +/- 1.82 mg.l-1 vs. 5.26 +/- 1.36 mg.l-1, p less than 0.001) after intake with food but this will probably not be of any clinical relevance. The product is considered to be of good sustained-release quality which in practice may well be taken with food in order to reduce the incidence of locally mediated theophylline-induced gastrointestinal disturbances.
在一项针对12名健康年轻成年人的双盲单剂量交叉实验中，研究了食物（早餐）对当药物以Dilatrane A.P. 400毫克胶囊（费森斯公司）（一种每日一次的缓释制剂）给药时茶碱吸收曲线和生物利用度的影响。该胶囊于上午8:00服用，要么在禁食10小时后，要么在摄入提供1990千焦能量的标准早餐后立即服用。通过高压液相色谱法在48小时内测定血浆中的茶碱。食物使达峰时间（tmax，9.4±1.3小时对8.4±1.7小时，均值±标准差）和曲线下面积（AUC0 - 48，114.3±41.7毫克·升⁻¹·小时对105.3±36.5毫克·升⁻¹·小时）略有增加，但不显著（p＞0.05，学生配对t检验），与空腹状态下服用胶囊相比，相对生物利用度为108.9±12.4%。进食后血浆中茶碱的最大浓度略有但显著升高（cmax，6.50±1.82毫克·升⁻¹对5.26±1.36毫克·升⁻¹，p＜0.001），但这可能在临床上并无相关性。该产品被认为具有良好的缓释质量，在实际应用中为了减少局部介导的茶碱引起的胃肠道紊乱的发生率，可以与食物一起服用。
