Retinoid absorption from simple and mixed micelles in the rat intestine.
The absorption of three retinoid analogs etretinate (ET), acitretin (ETA), and motretinid (MOE) from two distinct micellar systems was studied in the rat intestine. Each of the three drugs was loaded into simple micelles consisting of 10 mM sodium taurocholate (NaTC) and mixed micelles consisting of 10 mM egg phosphatidylcholine (PC) and 10 mM NaTC. Following perfusion through the jejunum segments, both the fraction of drug disappearing from the segment and the permeability of the drug from the lumen into the gut wall (Peff) was greater with the mixed micelles as compared to the simple micelles. Perfusion flow rate had an influence on the Peff for ET and ETA. Similar trends as for the jejunum were seen in the ileum perfusions. The simultaneous uptake of PC and NaTC during the retinoid perfusions was monitored. There appeared to be a correlation between the Peff values for PC and that of the retinoids. The viability of the in-situ perfusion system was confirmed histologically. There is evidence to indicate that the permeability of the intestine is sensitive to subtle differences in the chemical structure of the retinoids.
Pithavala
Y K
YK
Department of Pharmaceutics, University of Minnesota, Minneapolis 55455, USA.
Odishaw
J L
JL
Han
S
S
Wiedmann
T S
TS
Zimmerman
C L
CL
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D066298:In Vitro Techniques; D007408:Intestinal Absorption / Q000502:physiology*; D008297:Male; D008823:Micelles; D010539:Permeability; D051381:Rats; D017207:Rats, Sprague-Dawley; D012176:Retinoids / Q000737:chemistry / Q000493:pharmacokinetics*; D013056:Spectrophotometry, Ultraviolet; D013656:Taurocholic Acid / Q000032:analysis
D008823:Micelles; D012176:Retinoids; D013656:Taurocholic Acid