Enhancement by fatty acids of the rectal absorption of propranolol: in vitro evaluation in the rat.
The effects of a series of fatty acids on the rectal absorption of propranolol (PL) were examined in vitro, using macrogol 1500 base and rat rectal tissue. Lauric acid, at a fatty acid: PL molar ratio of 1:1, produced the largest increase in permeation rate (Js), penetration coefficient and partition coefficient of PL. PL flux was increased 2.5-fold in the presence of lauric acid compared to that without the fatty acid. However, the Js value of PL was decreased at increased molar ratios (e.g., 3:1) of lauric acid. The permeation rate of lauric acid across the rectal membrane was much larger than that of PL. Furthermore, the apparent partition coefficient of PL in an n-octanol/buffer system was significantly increased at a 1:1 molar ratio to lauric acid compared with that of PL alone. These results suggest that a complex-mediated mechanism facilitates PL transport, thereby partially contributing to the enhancement of PL rectal absorption. A similar mechanism is applicable to percutaneous drug absorption, as reported previously. Thus, a portion of PL, after first forming a complex with fatty acids, may rapidly permeate across rectal membranes.
Ogiso
T
T
Faculty of Pharmaceutical Sciences, Kinki University, Osaka, Japan.
Iwaki
M
M
Kashitani
Y
Y
Yamashita
K
K
D000818:Animals; D005227:Fatty Acids / Q000494:pharmacology*; D066298:In Vitro Techniques; D007408:Intestinal Absorption / Q000187:drug effects; D007850:Lauric Acids / Q000494:pharmacology; D008297:Male; D011092:Polyethylene Glycols; D011433:Propranolol / Q000493:pharmacokinetics*; D051381:Rats; D011919:Rats, Inbred Strains; D012007:Rectum / Q000187:drug effects / Q000378:metabolism*
D005227:Fatty Acids; D007850:Lauric Acids; C030358:lauric acid; D011092:Polyethylene Glycols; D011433:Propranolol