Diethyl ether fraction of Labrasol having a stronger absorption enhancing effect on gentamicin than Labrasol itself.
In our previous study, we had reported that Labrasol has a good gastrointestinal (GI) absorption enhancing effect on poorly absorbable drugs. In order to improve further absorption enhancing effect of Labrasol on gentamicin (GM), which is a representative water-soluble, poorly absorbable drug, Labrasol was fractionated with hexane, diethyl ether, ethyl acetate and water. The absorption enhancing effect of each fraction of Labrasol and Labrasol alone were evaluated in vivo using rats. Each test formulation of GM was administered into the rat colon at a dose of 5.0 mg/kg and plasma GM concentrations were measured by a HPLC method. Among the four fractions of Labrasol and Labrasol, diethyl ether fraction showed the strongest absorption enhancing effect on GM. When the doses of diethyl ether fraction were 1.0, 0.5 and 0.1 ml/kg, the Cmax values were 8.95 +/- 1.46, 8.02 +/- 2.14 and 7.41 +/- 1.25 microg/ml, respectively. Moreover, AUC(0-6) values were also maintained at high level, i.e. 27.28 +/- 5.90, 20.32 +/- 3.79 and 19.61 +/- 2.09 microg h/ml. Based on the AUC(0-6) values obtained with each fraction, the rank order of absorption enhancing effect on GM was diethyl ether > ethyl acetate=hexane > aqueous fraction.
Hu
Zhaopeng
Z
Department of Pharmacokinetics, Kyoto Pharmaceutical University, Yamashina-ku, Kyoto 607-8414, Japan. takada@mb.kyoto-phu.ac.jp
Prasad Yv
Rama
R
Tawa
Riichi
R
Konishi
Takahiro
T
Ishida
Makoto
M
Shibata
Nobuhito
N
Takada
Kanji
K
D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid; D004655:Emulsions / Q000737:chemistry* / Q000494:pharmacology*; D004986:Ether; D005839:Gentamicins / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005989:Glycerides; D007408:Intestinal Absorption / Q000187:drug effects*; D009391:Nephelometry and Turbidimetry; D009930:Organic Chemicals; D051381:Rats; D012997:Solvents; D013268:Stimulation, Chemical
D000900:Anti-Bacterial Agents; D004655:Emulsions; D005839:Gentamicins; D005989:Glycerides; D009930:Organic Chemicals; D012997:Solvents; C440220:Labrasol; D004986:Ether