Estimation of absorption enhancement by medium-chain fatty acids in rat large intestine.
The absorption enhancement by the sodium salts of several fatty acids was investigated in rat large intestine for model compounds having a wide range of molecular weight. Sodium caprylate (C8), sodium caprate (C10), sodium laurate (C12), which are categorized in medium-chain fatty acid, and sodium oleate (C18:1), long-chain unsaturated fatty acid, were employed as lipoidal adjuvants. Phenol red (MW=354.4), glycyrrhizin (822.9), fluorescein isothiocyanate-dextran-4 (FD-4, 4400), FD-10 (9400) and FD-40 (38900) were selected as model compounds for the assessment of the enhancing effect of the lipoidal adjuvants. The absorption of phenol red was promoted at the highest level, about 20 times higher by C12 and C18:1 than the control. The absorption rate - time profiles calculated by deconvolution method showed that C12 takes effect most rapidly and efficiently. In the case of glycyrrhizin, four adjuvants including C12 showed almost the same improvement of the absorption, about 30-40 times larger than the control. C8 and sodium citrate did not significantly enhance the absorption of those model compounds. For FD-4, FD-10 and FD-40, C10, C12 and C18:1 revealed almost the same enhancing effect and the absorption of FD-4, FD-10 and FD-40 was enhanced about 80 times, 1000-1800 times and about 200 times, respectively, larger than the control. The enhancement ratio, the ratio of AUC with adjuvant to AUC of control, suggests that these lipoidal adjuvants would improve most efficiently the absorption of the compound having the molecular weight of around 10000. Furthermore, C12 was suggested to be an effective adjuvant for the compounds with the wide range of molecular weight.
Higaki
K
K
Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Okayama University, Japan.
Yata
T
T
Sone
M
M
Ogawara
K
K
Kimura
T
T
D000277:Adjuvants, Pharmaceutic; D000818:Animals; D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid; D004396:Coloring Agents / Q000493:pharmacokinetics; D016503:Drug Delivery Systems; D005227:Fatty Acids / Q000494:pharmacology*; D019695:Glycyrrhizic Acid / Q000493:pharmacokinetics; D007408:Intestinal Absorption / Q000187:drug effects*; D007420:Intestine, Large / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010637:Phenolsulfonphthalein / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D013056:Spectrophotometry, Ultraviolet; D013268:Stimulation, Chemical
D000277:Adjuvants, Pharmaceutic; D004396:Coloring Agents; D005227:Fatty Acids; D019695:Glycyrrhizic Acid; D010637:Phenolsulfonphthalein