A quantitative concept of the mechanism of intestinal lymphatic transfer of lipophilic molecules.
The partition of mepitiostane, testosterone, and some structurally related compounds between lymph and blood in rat jejunum (lymph-blood partition ratio; LBPR) was determined, and the quantitative relationship between LBPR and lipophilicity was examined. When the delta Rm values (hydrophobic parameter derived from the mobility) relative to testosterone were < 0.2, their logLBPRs remained approximately constant in the range of -2 to -3. When the delta Rm values of the compounds were > 0.2, a linear correlation (r = 0.986, n = 8) was observed between these values and the logLBPRs. The LBPR, but not the extent of lymphatic absorption, of lipophilic molecules was determined strictly by the superlipophilicity, and for high partitioning into the lymph (> 50% of the absorbed amount), the delta Rm value had to be > 0.50 (5.65 as the logP value). The relationship between LBPR and superlipophilicity could be explained on the basis of the theoretical equations derived from absorption kinetics based on a dynamic partitioning model.
Ichihashi
T
T
Shionogi Research Laboratories, Shionogi & Co., Ltd., Osaka, Japan.
Nagasaki
T
T
Takagishi
Y
Y
Yamada
H
H
D045930:Anabolic Agents / Q000737:chemistry / Q000493:pharmacokinetics; D000732:Androstanols / Q000737:chemistry / Q000493:pharmacokinetics; D000818:Animals; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002855:Chromatography, Thin Layer; D005260:Female; D066298:In Vitro Techniques; D007408:Intestinal Absorption / Q000502:physiology*; D007583:Jejunum / Q000378:metabolism*; D008055:Lipids / Q000097:blood / Q000737:chemistry; D008208:Lymphatic System / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D013739:Testosterone / Q000737:chemistry / Q000493:pharmacokinetics
D045930:Anabolic Agents; D000732:Androstanols; D008055:Lipids; D013739:Testosterone; C006242:mepitiostane