Influence of hydrodynamics and particle size on the absorption of felodipine in labradors.
OBJECTIVE
To study the influence of GI hydrodynamics and drug particle size on felodipine absorption in the dog.


METHODS
Labradors fistulated at midjejunum were used to selectively study the influence of hydrodynamics and particle size on the in vivo dissolution and absorption of the poorly soluble, lipophilic drug felodipine. A combination of infusion and oral administration of either normal saline or a 5% glucose solution was used to maintain "fasted" and establish "fed" state motility patterns, respectively. The absorption characteristics of both a micronized (8 microm) and a coarse fraction (125 micom) of felodipine were subsequently studied under these two motility patterns.


RESULTS
A reduction in particle size led up to an approximate 22-fold increase in maximum plasma concentration and up to an approximate 14-fold increase in area under the curve, with a commensurate decrease in the time at which the maximum plasma concentration occurred. Although the absorption of felodipine from the solution and micronized suspension was not influenced by a change in the hydrodynamics, felodipine was absorbed from the coarse suspension almost twice as well in the "fed" state as under "fasted" conditions.


CONCLUSIONS
Absorption from coarse suspensions of felodipine was sensitive to luminal hydrodynamics, whereas micronized suspensions were not. However, the particle size seems to have a much more important influence on the bioavailability of felodipine than the hydrodynamics per se.
Scholz
Annette
A
Institut für Pharmazeutische Technologie, Johann Wolfgang Goethe-Universität, Frankfurt am Main, Germany.
Abrahamsson
Bertil
B
Diebold
Steffen M
SM
Kostewicz
Edmund
E
Polentarutti
Britta I
BI
Ungell
Anna-Lena
AL
Dressman
Jennifer B
JB
D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D004285:Dogs; D005215:Fasting; D015736:Felodipine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D007408:Intestinal Absorption; D008297:Male; D010316:Particle Size; D011208:Powders; D012995:Solubility; D012996:Solutions; D013535:Suspensions
D011208:Powders; D012996:Solutions; D013535:Suspensions; D015736:Felodipine