[Effects of absorption enhancers on intestinal absorption of lumbrokinase].
OBJECTIVE
To explore the intestinal absorption characteristics of lumbrokinase (YJM-I) in the absence or presence of various absorption enhancers and to find the optimum intestinal site for YJM-I absorption.


METHODS
The absorption kinetics and absorption intestinal sites for YJM-I absorption were investigated with the method of diffusion cell in vitro, duodenum bolus injection, recirculating perfusion and in situ duodenum perfusion in vivo.


RESULTS
YJM-I could be transported into blood and kept its biological activity across intestinal endothelial membrane after administration via duodenum site, whereas with lower bioavailability. Some of the absorption enhancers were shown good enhancement effects on intestinal absorption of YJM-I in vitro and in situ experiments. The order of enhanced efficiencies of various enhancers on duodenum, ileum and jejunum in vitro permeation experiments were shown as follows: 1% chitosan > 1% SDCh > 1% Na2EDTA > 1% SDS > 1% sodium caprylate > 1% poloxamer > 1% HP-beta-CD. The order of enhanced efficiencies of various enhancers on duodenum absorption of YJM-I in vivo were as follows: 2.5% SDCh > 2.5% Na2EDTA > 2.0% chitosan > 2.5% SDS > 2.5% sodium caprylate > 2.5% Poloxamer > 2.5% HP-beta-CD.


CONCLUSIONS
The results indicated that the absorption of YJM-I could be enhanced by various enhancers, and duodenum was the optimum absorption site of YJM-I. Furthermore, bio-adhesive chitosan might be a potential enhancer of intestinal YJM-I absorption.
Li
Yu-Hua
YH
School of Pharmaceutical Sciences, Peking University, Beijing 100083, China.
Zhang
Mo
M
Wang
Jian-Cheng
JC
Zhang
Shu
S
Liu
Jian-Rong
JR
Zhang
Qiang
Q
D000284:Administration, Oral; D000818:Animals; D019540:Area Under Curve; D002210:Caprylates / Q000494:pharmacology; D048271:Chitosan / Q000494:pharmacology; D003840:Deoxycholic Acid / Q000494:pharmacology; D004386:Duodenum / Q000187:drug effects / Q000378:metabolism*; D004492:Edetic Acid / Q000494:pharmacology; D010450:Endopeptidases / Q000008:administration & dosage / Q000493:pharmacokinetics*; D007275:Injections, Intravenous; D007408:Intestinal Absorption; D008297:Male; D008657:Metabolic Clearance Rate; D020442:Poloxamer / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D002210:Caprylates; D003840:Deoxycholic Acid; D020442:Poloxamer; D048271:Chitosan; D004492:Edetic Acid; D010450:Endopeptidases; C083421:lumbrokinase; C031492:octanoic acid