Effect of colestipol on indomethacin pharmacokinetics in rabbits

ABSTRACT

The purpose of this investigation was to determine whether the oral administration of colestipol would increase the systemic elimination of indomethacin following intravenous administration [2mg/kg] to rabbits. Adsorption studies in-vitro were also performed. The in-vivo results indicate that colestipol do not affect the serum levels of indomethacin. The values during colestipol treatment colestipol do not affect the serum levels of indomethanic. The values during colestipol treatment were lower than those for the control, but the differences in concentrations were not significant. No significant differences were observed in any of the calculated pharmacokinetic parameters between the control and colestipol treated rabbits. This in-vitro adsorption studies supported the in-vivo results. colestipol was found to have a poor adsorption capacity for indomethacin. The Freundlich constant [K] for adsorption was 0.9mg/g at equilibrium [3h]. Furthermore, three successive washings of the drug- adsorbent mixture, with 20 mL buffer solution, resulted in 33.8% desorption. Based on the in-vivo andin-vitro studies it is not likely that the administration of colestipol will result in a change in the pharmacokinetic parameters of indomethanin in man