Jonkman J H
Pharma Bio-Research International B.V., Assen, Groningen, The Netherlands.
Clin Pharmacokinet. 1989 Mar;16(3):162-79. doi: 10.2165/00003088-198916030-00003.
Currently, theophylline is being used predominantly as sustained-release capsules or tablets. In the mid-seventies the first preparations for use with a dosage interval of 12 hours (twice-daily preparations) were introduced. Since 1983, theophylline preparations that can be given with an interval of 24 hours (once-daily preparations) have become available. The release of theophylline from some of these products can be influenced (either increased or decreased) by concomitant intake of food. With some preparations the composition of the meal (especially the fat content) has an influence on the degree of effect. The consequence may be an effect on the rate of absorption or on the amount absorbed, or both simultaneously. This could result in an unexpected shift of the plasma theophylline concentration. Such a shift is therapeutically undesirable, because theophylline has a fairly narrow therapeutic range. A review is given of those food interactions with the sustained-release theophylline preparations, both twice-daily and once-daily products, that are currently on the world market. Special attention is paid to the specific (bio)pharmaceutical characteristics of the different products, and to the influence of the composition and timing of the meals. For each preparation the effect of food on the following pharmacokinetic parameters is discussed: area under the plasma concentration-time curve, peak plasma drug concentration and time to reach this peak. Where possible, the results for both adults and children are discussed. There are indications that children are more susceptible to food-effects than adults. The regulatory aspects are mentioned briefly. Clinically important effects of food have been observed with the following twice-daily products: 'Theo-Dur Sprinkle', 'Theolair SR' (= 'Nuelin SR') and 'Theograd'. Pronounced effects could have an even greater impact with once-daily preparations, as the total daily dose will be given at a single time. A particularly sudden release of a major part of the dose ('dose-dumping') may result in toxic plasma concentrations. Among these products, clinically important effects in children have been reported with 'Theo-24' and 'Uniphyl'.
目前，茶碱主要以缓释胶囊或片剂的形式使用。20世纪70年代中期，首次推出了给药间隔为12小时的制剂（每日两次制剂）。自1983年以来，可每24小时给药一次的茶碱制剂（每日一次制剂）已上市。其中一些产品中茶碱的释放会受到同时摄入食物的影响（增加或减少）。对于某些制剂，膳食的组成（尤其是脂肪含量）会对效果程度产生影响。其结果可能会对吸收速率或吸收量产生影响，或者同时对两者产生影响。这可能会导致血浆茶碱浓度意外变化。这种变化在治疗上是不可取的，因为茶碱的治疗范围相当窄。本文综述了目前在世界市场上销售的与缓释茶碱制剂（包括每日两次和每日一次产品）存在的食物相互作用。特别关注了不同产品的具体（生物）药学特性，以及膳食组成和进食时间的影响。针对每种制剂，讨论了食物对以下药代动力学参数的影响：血浆浓度-时间曲线下面积、血浆药物峰浓度以及达到该峰浓度的时间。在可能的情况下，还讨论了成人和儿童的结果。有迹象表明，儿童比成人更容易受到食物影响。文中简要提及了监管方面的情况。已观察到以下每日两次产品与食物之间存在临床重要影响：“Theo-Dur Sprinkle”、“Theolair SR”（=“Nuelin SR”）和“Theograd”。对于每日一次制剂，显著的影响可能会产生更大的作用，因为每日总剂量将在单次给药时给予。剂量的一大部分特别突然的释放（“剂量倾泻”）可能会导致血浆中毒浓度。在这些产品中，已报道“Theo-24”和“Uniphyl”在儿童中存在临床重要影响。
