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Pharmacokinetics of chitobiose and chitotriose administered intravenously or orally to rats.

Chitooligosaccharides have attracted much attention as new biomedical materials. The biologic availability of each of these chitooligosaccharides, however, has not yet been studied. In the present study, we found that chitobiose and chitotriose appeared in the blood of rats with maximum plasma concentrations at around 1 h after administration when given orally at a dose of 30 mg/kg. However, chitotetraose and chitopentaose did not appear in the blood when given at a dose of 300 mg/kg. Pharmacokinetic analysis of chitobiose and chitotriose after intravenous administration at 100 mg/kg revealed that both sugars were eliminated from the body following a one-compartment model and that the former relative to the latter was higher for both the total body clearance (224+/-43 vs. 155+/-26 ml/h/kg) and the distribution volume (107+/-15 vs. 65+/-9 ml/kg). The absolute oral bioavailability of chitobiose was higher than that of chitotriose at all doses (30, 100, and 300 mg/kg) examined. The first-order absorption rate constants for chitobiose and chitotriose at all doses were less than 1.0 h(-1) and smaller than the elimination rate constants (2.2+/-0.3, 2.7+/-0.1 h(-1), respectively). The absorption was slow, resulting in flip-flop kinetics. This study indicates that among various chitooligosaccharides, only chitobiose and chitotriose can be appreciably absorbed from the gastrointestinal tract.