IMPROVED ORAL BIOAVAILABILITY OF PROPRANOLOL IN HEALTHY-HUMAN VOLUNTEERS USING A LIVER BYPASS DRUG DELIVERY SYSTEM CONTAINING OLEIC-ACID

被引:21
作者
BARNWELL, SG
LAUDANSKI, T
STORY, MJ
MALLINSON, CB
HARRIS, RJ
COLE, SK
KEATING, M
ATTWOOD, D
机构
[1] UNIV MANCHESTER, DEPT PHARM, MANCHESTER M13 9PL, LANCS, ENGLAND
[2] MED ACAD BIALYSTOK, INST OBSTET & GYNAECOL, PL-15062 BIALYSTOK, POLAND
关键词
LYMPHATIC ABSORPTION; ENTERIC-COATED LIQUID-FILLED HARD GELATIN CAPSULES; PROPRANOLOL; OLEIC ACID; DRUG DELIVERY;
D O I
10.1016/0378-5173(92)90342-Y
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Propranolol, a clinically proven lipophilic beta-adrenergic blocking agent, undergoes extensive and unpredictable first-pass hepatic metabolism when administered as a conventional oral formulation. A nine-subject three-way cross-over study was performed in healthy human volunteers to assess the relative bioavailability of two novel oral formulations of propranolol, designed to bypass hepatic first-pass metabolism. These formulations contained a mixture of unsaturated fatty acids, mainly oleic acid, and surfactants in enteric-coated liquid-filled hard gelatin capsules. Using these formulations selective increases of up to more than 6-fold in AUC and 4-fold in C(max) were achieved in subjects who responded poorly to Inderal(R). The increased propranolol bioavailability achieved using the liver bypass formulations was associated with a reduction in the coefficient of variance for both C(max) and AUC of up to 44%, when compared to Inderal(R). The results of the present study suggest the possibility of developing a predictable reduced dose delivery system for basic lipophilic drugs which undergo extensive hepatic first-pass metabolism.
引用
收藏
页码:423 / 432
页数:10
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