Enhanced intestinal absorption of vancomycin with Labrasol and D-alpha-tocopheryl PEG 1000 succinate in rats.
Vancomycin hydrochloride (VCM) is a glycopeptide antibiotic used for the treatment of infections caused by methicillin-resistant staphylococci. It is water soluble, having a high molecular weight, and poorly absorbed from the gastrointestinal tract. Mixtures of VCM with Labrasol and D-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS) were prepared to improve oral absorption of VCM. Administration of VCM solution to rat ileum at a dose of 20 mg/kg did not result in detectable plasma VCM concentration. Formulation containing 50% of Labrasol resulted in a Cmax value of 5.86+/-0.97 microg/ml and an AUC(0-6h) value of 16.06+/-1.78 microgh/ml. Addition of TPGS to VCM solution at 12.5% concentration also increased the plasma VCM concentration with a Cmax value of 4.98+/-0.45 microg/ml. But the AUC(0-6 h) (9.87+/-1.90 microgh/ml) was significantly lower than that obtained with Labrasol. The addition of 5.0 and 25.0% TPGS to solutions of VCM containing 50% of Labrasol did not result in any significant increase either in Cmax or AUC(0-6 h) of VCM. Whereas the addition of 12.5% of TPGS has resulted in an increase in Cmax and AUC(0-6 h) by 2.2 and 2.4 times, respectively, suggesting that this concentration of 50% Labrasol and 12.5% TPGS (1:0.25) was optimum for improving intestinal absorption of VCM. A dose dependent decrease in the Cmax and AUC(0-6 h) values was observed when the dose of absorption enhancers was decreased by 50% with formulation containing Labrasol and TPGS in 1:0.25 ratio. The results of the study indicate that formulations containing Labrasol and TPGS improve intestinal absorption of hydrophilic macromolecular drug, VCM.
Prasad
Y V Rama
YV
Department of Pharmacokinetics, Kyoto Pharmaceutical University, Yamashina-ku, Kyoto 607-8414, Japan. drprasadyv@yahoo.com
Puthli
S P
SP
Eaimtrakarn
Sudarat
S
Ishida
Makoto
M
Yoshikawa
Yukako
Y
Shibata
Nobuhito
N
Takada
Kanji
K
D000818:Animals; D019540:Area Under Curve; D004655:Emulsions / Q000008:administration & dosage*; D005989:Glycerides; D007408:Intestinal Absorption; D008297:Male; D009930:Organic Chemicals; D011092:Polyethylene Glycols; D051381:Rats; D017208:Rats, Wistar; D014640:Vancomycin / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D014810:Vitamin E / Q000008:administration & dosage* / Q000031:analogs & derivatives*
D004655:Emulsions; D005989:Glycerides; D009930:Organic Chemicals; C440220:Labrasol; D014810:Vitamin E; D011092:Polyethylene Glycols; D014640:Vancomycin; C014225:tocophersolan