Hendeles L, Weinberger M
J Allergy Clin Immunol. 1985 Aug;76(2 Pt 2):285-91. doi: 10.1016/0091-6749(85)90643-8.
Unless they are taken at unacceptably frequent intervals, conventional rapid-release theophylline tablets and liquids produce excessive serum concentration fluctuations, particularly in patients with rapid elimination. Slow-release formulations provide more stable serum concentrations with longer dosing intervals if absorbed completely, consistently, and at a sufficiently slow rate and thus have the potential to improve efficacy and compliance. However, there are clinically important differences in the extent and rate of absorption among the 15 slow-release formulations available under 29 brand names in the United States. Fluctuations in steady-state serum concentrations are a function of the absorption rate of the product, the elimination rate of the patient, and the dosing interval. In patients with slow elimination, clinically relevant differences among formulations are not apparent with twice-daily dosing. Among patients with more rapid elimination, however, available data for only two products demonstrate sufficiently slow absorption to justify routine twice-daily use without excessive fluctuations. More rapidly absorbed formulations must be administered at 8-hour intervals in such patients to prevent breakthrough in asthmatic symptoms before the next dose, despite promotional claims to the contrary. Current products approved for "once-a-day" dosing are clinically inadequate because of incomplete or erratic absorption or excessive serum concentration fluctuations. Lastly, food intake induces dose dumping of potentially toxic amounts of theophylline from Theo-24 and greatly impairs absorption from Theo-Dur Sprinkle capsules but has no important effect on Theo-Dur tablets. The effects of food on most other theophylline products are not known.
除非以不可接受的频繁间隔服用，传统的速释型茶碱片剂和液体制剂会导致血清浓度过度波动，尤其是在消除速度较快的患者中。如果缓释制剂能完全、持续且以足够慢的速度被吸收，那么它能在更长的给药间隔下提供更稳定的血清浓度，因此有提高疗效和依从性的潜力。然而，在美国有29个品牌的15种缓释制剂，它们在吸收程度和速度上存在临床上的重要差异。稳态血清浓度的波动取决于产品的吸收速度、患者的消除速度和给药间隔。在消除速度慢的患者中，每日两次给药时，不同制剂之间临床上相关的差异并不明显。然而，在消除速度较快的患者中，仅有两种产品的现有数据表明其吸收足够慢，足以证明常规每日两次使用不会出现过度波动。在这类患者中，吸收较快的制剂必须每8小时给药一次，以防止在下一剂之前哮喘症状发作，尽管有相反的促销宣传。目前被批准用于“每日一次”给药的产品在临床上并不充分，因为吸收不完全或不稳定，或者血清浓度波动过大。最后，食物摄入会导致Theo-24中潜在有毒量的茶碱剂量倾泻，并极大地损害Theo-Dur Sprinkle胶囊的吸收，但对Theo-Dur片剂没有重要影响。食物对大多数其他茶碱产品的影响尚不清楚。
