Single dose pharmacokinetics and bioavailability of butyryl glucosamine in the rat

To study single dose pharmacokinetics and bioavailability of the synthetic glucosamine analogue, N-butyryl glucosamine (GLcNBu) after different routes of administration, and also the effect of food following oral doses of GLcNBu in the rat, and stability and absorption of GLcNBu across the rat everted intestine.

GLcNBu was administered intravenously (i.v.), intraperitoneally (i.p.) and orally. Effect of food was studied following oral administration only. Single doses of 223 mg/kg were administered in all cases. Serial blood samples were collected from the jugular vein for GLcNBu determination. Everted excised rat intestine segments were suspended in Tris buffer at 37 degrees C and samples collected from both serosal and mucosal sides. GLcNBu was measured using HPLC.

Following i.v. administration, the terminal half-life was 0.29 -/+ 0.06 h, volume of distribution at steady state was 2.1 -/+ 0.26 L/kg and total body clearance was 5.23 -/+ 1.44 L/h/kg. Bioavailability was less than 17% and 100% following oral and i.p. doses respectively. GLcNBu was rapidly absorbed after oral doses (Tmax, 29-40 min). Food had no significant effect on the pharmacokinetics of GLcNBu. There was no evidence of breakdown of GLcNBu in the presence of everted intestine. The mucosal to serosal transport of GLcNBu was about 20% after 2 h incubation.

GLcNBu has rapid but low absorption and is widely distributed and efficiently cleared. The gut rather than liver is mainly responsible for the low bioavailability of GLcNBu. Limited absorption of GLcNBu suggests a transport dependent absorption. Food does not significantly affect the bioavailability of GLcNBu.