Drewe J, Mazer N, Abisch E, Krummen K, Keck M
Drug Delivery System Department, Sandoz, Basle, Switzerland.
Eur J Clin Pharmacol. 1988;35(5):535-41. doi: 10.1007/BF00558250.
The influence of food on release of drug from a modified release capsule of bromocriptine 5 mg (Parlodel SRO) and a conventional formulation of bromocriptine 5 mg has been studied in 8 healthy male volunteers. Both formulations produced objective and subjective effects, such as orthostatic reactions, nausea, dizziness, vomiting and nasal congestion. The modified release capsule caused fewer side-effects than the normal capsule. Both formulations had less cardiovascular effect in the fed than in the fasting state. There was no significant difference between the normal and the modified release capsules taken fasting or after a meal in terms of the AUC extrapolated to infinity. The relative bioavailability of the 5 mg modified release capsule was 84.6% of the normal capsule under fasting conditions and 107.5% after food. In contrast to the virtually unchanged extent of absorption, the rate of absorption was markedly affected by food, especially from the conventional capsule. The mean time of 50% absorption increased from 1.06 h (fasting) to 3.2 h (fed), whereas for the modified release capsule food mainly resulted in an increased lag time of absorption. The almost instantaneous dissolution of bromocriptine from the normal capsule in vitro (both in HCl and fasting human gastric juice) and the delay of absorption after a meal in vivo suggest that the rate limiting step in absorption of the normal capsules is delivery of released drug from the stomach to the small intestine, which is delayed by food. Both the modified release 5-mg capsule and the normal 5-mg capsule showed extended suppression of prolactin over 36 h, in all subjects, both fasted and after a meal.
在8名健康男性志愿者中研究了食物对5毫克溴隐亭缓释胶囊（Parlodel SRO）和5毫克溴隐亭常规制剂药物释放的影响。两种制剂均产生了客观和主观效应，如体位性反应、恶心、头晕、呕吐和鼻塞。缓释胶囊引起的副作用比普通胶囊少。两种制剂在进食状态下的心血管效应均比空腹状态下小。空腹或餐后服用普通胶囊和缓释胶囊，外推至无穷大的AUC无显著差异。5毫克缓释胶囊在空腹条件下的相对生物利用度为普通胶囊的84.6%，进食后为107.5%。与吸收程度几乎不变形成对比的是，食物对吸收速率有显著影响，尤其是对常规胶囊。50%吸收的平均时间从1.06小时（空腹）增加到3.2小时（进食），而对于缓释胶囊，食物主要导致吸收的延迟时间增加。溴隐亭在体外（在盐酸和空腹人胃液中）从普通胶囊几乎瞬间溶解，而进食后体内吸收延迟，这表明普通胶囊吸收的限速步骤是释放的药物从胃输送到小肠，而食物会延迟这一过程。5毫克缓释胶囊和5毫克普通胶囊在所有受试者（无论空腹还是进食后）中均显示出对催乳素的持续抑制作用超过36小时。
