Evaluation of oral formulations of gentamicin containing labrasol in beagle dogs.
Gentamicin (GM) is a polarized water-soluble compound having very poor intestinal membrane permeability resulting in low oral bioavailability. Labrasol was found to improve the intestinal absorption of GM in rats. In the present study, GM formulations containing labrasol were evaluated in beagle dogs after filling into hydroxypropylmethyl cellulose (HPMC) capsules wrapped with Eudragit L100 (Eud L) and Eudragit S100 (Eud S) films. The results of the in vitro drug release studies could not differentiate between two kinds of enteric capsules and among the three kinds of GM formulations. Oral administration of GM solution at a dose of 50.0 mg per dog of GM and 0.60 ml per dog of labrasol has resulted in Cmax values of 2.38 +/- 0.50 microg/ml and 2.30 +/- 0.42 microg/ml with Eud L and Eud S capsules, respectively. The AUC values obtained were also higher at 4.35 +/- 1.31 microg h/ml and 5.34 +/- 0.95 microg h/ml with Eud L and Eud S capsules, respectively. Formulation of GM as a suspension in labrasol has resulted in the decrease of Cmax values by two to four times and AUC values by > 2.5 times compared to the solution formulation. The above results indicate that solution formulation was better over the suspension. An absorbent, synthetic sponge was used to absorb GM solution formulation and encapsulated with Eud L and Eud S capsules. The Cmax and AUC values obtained with sponge formulation were higher than those of suspension formulations but were lower than solution formulations. There was no significant difference in the extent of GM absorption between Eud L and Eud S capsules used for encapsulating GM formulations.
Rama Prasad
Y V
YV
Department of Pharmacokinetics, Kyoto Pharmaceutical University, Yamashina-ku, Kyoto 607-8414, Japan. drprasadyv@yahoo.com
Eaimtrakarn
Sudarat
S
Ishida
Makoto
M
Kusawake
Yoichi
Y
Tawa
Riichi
R
Yoshikawa
Yukako
Y
Shibata
Nobuhito
N
Takada
Kanji
K
D000284:Administration, Oral; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D019540:Area Under Curve; D002214:Capsules; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D004285:Dogs; D004338:Drug Combinations; D016503:Drug Delivery Systems; D004655:Emulsions / Q000493:pharmacokinetics*; D005839:Gentamicins / Q000008:administration & dosage* / Q000493:pharmacokinetics; D005989:Glycerides; D007408:Intestinal Absorption / Q000187:drug effects*; D009930:Organic Chemicals
D000900:Anti-Bacterial Agents; D002214:Capsules; D004338:Drug Combinations; D004655:Emulsions; D005839:Gentamicins; D005989:Glycerides; D009930:Organic Chemicals; C440220:Labrasol