De Mey C, Meineke I
SK&F-Institute of Applied Clinical Pharmacology, Göttingen, Germany.
Br J Clin Pharmacol. 1992 Feb;33(2):179-82. doi: 10.1111/j.1365-2125.1992.tb04021.x.
Plasma and urine concentrations of 5-ASA and its N-acetyl metabolite 5-AcASA were measured over 48 h in 12 young healthy male subjects, who received three doses of three times enteric coated 500 mg 5-ASA tablets at 7 h interval, on two occasions 14 days apart. On one occasion the doses were given after standard meals; on the other occasion, they were given 1 h before meals. Administration of the tablets after meals delayed systemic drug absorption but did not affect the extent of absorption. There was a sharp rise in the plasma concentrations of 5-ASA and 5-AcASA in the early morning (i.e. circa 24 h after administration of the 1st dose) independent of when the tablets were taken with respect to the meals. This suggests that tablets or tablet fragments remained in the stomach until the later part of the night. Thus, diurnal effects may be more important than prandial effects in the evaluation of the kinetics of 5-ASA and its metabolites after peroral administration of enteric coated tablets.
在12名年轻健康男性受试者中,每隔7小时服用三剂500毫克肠溶包衣5 - 氨基水杨酸(5 - ASA)片剂,共服用三次,在间隔14天的两个时间段进行,测定48小时内血浆和尿液中5 - ASA及其N - 乙酰代谢物5 - 乙酰氨基水杨酸(5 - AcASA)的浓度。一次是在标准餐后给药;另一次是在餐前1小时给药。餐后给药延迟了药物的全身吸收,但不影响吸收程度。清晨时(即大约在服用第一剂后24小时),5 - ASA和5 - AcASA的血浆浓度急剧上升,与片剂相对于餐食的服用时间无关。这表明片剂或片剂碎片在胃中一直留存到深夜。因此,在评估口服肠溶包衣片剂后5 - ASA及其代谢物的动力学时,昼夜效应可能比餐时效应更重要。