Rhie J K, Hayashi Y, Welage L S, Frens J, Wald R J, Barnett J L, Amidon G E, Putcha L, Amidon G L
University of Michigan, College of Pharmacy, Ann Arbor, USA.
Pharm Res. 1998 Feb;15(2):233-8. doi: 10.1023/a:1011962501270.
The objective of this study was to evaluate drug marker absorption in relation to the gastric emptying (GE) of 0.7 mm and 3.6 mm enteric coated pellets as a function of viscosity and the underlying gastric motility.
Twelve subjects were evaluated in a 3-way crossover study. 0.7 mm caffeine and 3.6 mm acetaminophen enteric coated pellets were concurrently administered with a viscous caloric meal at the levels of 4000, 6000 and 8000 cP. Gastric motility was simultaneously measured with antral manometry and compared to time events in the plasma profiles of the drug markers.
Caffeine, from the 0.7 mm pellets, was observed significantly earlier in the plasma than acetaminophen, from the 3.6 mm pellets, at all levels of viscosity. Motility related size differentiated GE was consistently observed at all viscosity levels, however, less variability was observed with the 4000 cP meal. Specifically, the onset of absorption from the of 3.6 mm pellets correlated with the onset of Phase II fasted state contractions (r = 0.929, p < 0.01).
The timeframe of drug marker absorption and the onset of motility events were not altered within the range of viscosities evaluated. Rather, the differences in drug marker profiles from the non-digestible solids were most likely the result of the interaction between viscosity and motility influencing antral flow dynamics. The administration of the two sizes of pellets and a viscous caloric meal with subsequent monitoring of drug marker profiles is useful as a reference to assess the influence of motility patterns on the absorption profile of orally administered agents.
本研究的目的是评估0.7毫米和3.6毫米肠溶包衣微丸的药物标记物吸收与胃排空（GE）的关系，该关系是粘度和潜在胃动力的函数。
在一项三交叉研究中对12名受试者进行了评估。0.7毫米咖啡因和3.6毫米对乙酰氨基酚肠溶包衣微丸与4000、6000和8000厘泊水平的粘性高热量餐同时给药。通过胃窦测压法同时测量胃动力，并与药物标记物血浆谱中的时间事件进行比较。
在所有粘度水平下，血浆中观察到来自0.7毫米微丸的咖啡因明显早于来自3.6毫米微丸的对乙酰氨基酚。在所有粘度水平下均持续观察到与动力相关的大小差异对胃排空的影响，然而，4000厘泊餐的变异性较小。具体而言，来自3.6毫米微丸的吸收开始与II期禁食状态收缩的开始相关（r = 0.929，p < 0.01）。
在所评估的粘度范围内，药物标记物吸收的时间范围和动力事件的开始没有改变。相反，来自不可消化固体的药物标记物谱的差异很可能是粘度和动力之间相互作用影响胃窦流动动力学的结果。同时给予两种大小的微丸和粘性高热量餐，随后监测药物标记物谱，可作为评估动力模式对口服制剂吸收谱影响的参考。
