DOSE-DEPENDENT INTESTINAL-ABSORPTION AND SIGNIFICANT INTESTINAL EXCRETION (EXSORPTION) OF THE BETA-BLOCKER PAFENOLOL IN THE RAT

被引:37
作者
LENNERNAS, H [1 ]
REGARDH, CG [1 ]
机构
[1] ASTRA HASSLE AB,DEPT PHARMACOKINET & DRUG METAB CARDIOVASC RES,MOLNDAL,SWEDEN
关键词
PHARMACOKINETICS; DOUBLE PEAKS; DOSE-DEPENDENT ABSORPTION; INTESTINAL EXCRETION; EXSORPTION;
D O I
10.1023/A:1018916017723
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
The elimination of [H-3]pafenolol and metabolites was investigated in fasted and fed rats. Separate groups received intravenous doses (0.3 and 3.0 mumol/kg) and oral doses (1 and 25 mumol/kg). After iv administration of pafenolol, the excretion of unchanged drug into urine and feces was about 50 and 25-30% of the given dose, respectively. The predominating mechanism for the excretion of pafenolol into feces was intestinal excretion (exsorption) directly from blood into gut lumen, since only about 3% of a given iv dose was recovered as pafenolol in the bile. When the oral dose was raised from 1 to 25 mumol/kg, the mean (+/-SD) bioavailability, calculated from urine data, increased from 14 +/- 9 to 30 +/- 11% (P < 0.05) in the starved rats and from 14 +/- 3 to 16 +/- 3% in the fed animals. In parallel, the fraction absorbed from the gut (f(a)) increased from 19 +/- 9 to 31 +/- 10% in the starved rats and from 16 +/- 4 to 19 +/- 5% in the fed animals, respectively. This indicates that the low bioavailability is due primarily to poor intestinal uptake.
引用
收藏
页码:727 / 731
页数:5
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