Evaluation of the Intelisite capsule to deliver theophylline and frusemide tablets to the small intestine and colon

被引:41
作者
Clear, NJ
Milton, A
Humphrey, M
Henry, BT
Wulff, M
Nichols, DJ
Anziano, RJ
Wilding, I
机构
[1] Pfizer Ltd, Cent Res, Pharmaceut Res & Dev, Sandwich CT13 9NJ, Kent, England
[2] Pfizer Ltd, Cent Res, Early Clin Res Grp, Sandwich CT13 9NJ, Kent, England
[3] Pfizer Inc, Cent Res, Biometr, Groton, CT 06340 USA
[4] Pharmaceut Profiles, Nottingham NG11 6JS, England
关键词
non-invasive regional drug delivery; intestinal and colonic drug absorption theophylline; frusemide;
D O I
10.1016/S0928-0987(01)00134-8
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The objective of the research was to establish the capability of the Intelisite capsule to deliver the probe drugs, theophylline and frusemide, in the form of split immediate release (IR) tablets, to the small intestine and colon. The two probe drugs were administered together in an open, random, three-way crossover study in eight healthy volunteers, comparing absorption following Intelisite: delivery in the small bowel and colon to conventional IR dosing. Gamma scintigraphy was employed to monitor the gastrointestinal transit and activation of the Intelisite capsule. Standard pharmacokinetic parameters, and the percentage remaining in the capsules post defecation were determined. The Intelisite capsule was well tolerated in human volunteers and successfully activated on 15/16 occasions. Pharmacoscintigraphy showed internal marker release from the Intelisite capsule to be similar to 10-fold faster in the small intestine than in the colon. Theophylline and frusemide were both well absorbed following Intelisite activation in the small intestine, whereas complete colonic absorption was only observed in 1/7 subjects for theophylline, and 0/7 subjects for frusemide. The probe drugs were successfully delivered in particulate form from the Intelisite capsule in the small intestine and produced expected pharmacokinetic profiles. However drug release in the colon was incomplete and variable possibly due to: low water content, poor mixing, and a high loading dose. (C) 2001 Published by Elsevier Science B.V.
引用
收藏
页码:375 / 384
页数:10
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