Absorption and tissue distribution of a novel carboxymethyldextran after oral administration

作者：Charef Said^*; Papy Garcia Dulce; Courty Jose

来源：Biomedicine & Pharmacotherapy, 2010, 64(9): 627-632.

DOI：10.1016/j.biopha.2010.03.002

• Pharmacokinetic
• Dextran
• Oral absorption

The aim of this study was to investigate the development of an oral dextran derivative OTR4120. Pharmacokinetics (PK) parameters of OTR4120 were determined after treatment with intravenous injection (i.v.) at dose 5 mg/kg, intraperitoneal injection (i.p.) at dose 50 mg/kg or oral administration at dose 70 mg/kg. To study distribution at dose 70 mg/kg after oral administration, OTR4120 was given by gavage to mice. In ex vivo experiments, SDS-PAGE showed that plasma of mice treated orally at dose 70 mg/kg induced the formation of covalently linked complexes between antithrombin III and thrombin. OTR4120 were absorbed and metabolized following oral administration. OTR4120 given i.v., i.p. and oral had relatively small volume of distribution 0.95 L/kg and 4.68 L/kg respectively, plasma clearance was 45, 520 and 514 ml/h per kg after i.v., i.p. or oral administration respectively. Short elimination half-life was 80 min after i.p. administration and 383 min after oral administration. OTR4120 was distributed in the spleen and kidney and accumulated there over a long period, whereas the OTR4120 levels in liver were negligible a 24 hours after oral administration. Food do not change the oral bioavailability of OTR4120 in mice, AUC, C-max and T-max of OTR4120 were not significantly different when mice received the oral dose with food compared with under fasting conditions. This work presents another therapeutic agents administration way using dextran delivery system.

• 出版日期2010-11