effect of omeprazole on pharmacokinetics of methadone in the rabbits

Omeprazole is a gastric H [+] K [+]ATPase acid pump inhibitor, increases gastric pH and metabolized in microsomal enzyme system in liver. Pharmacokinetic interaction of methadone with omeprazole was investigated first time in rabbits. Fifteen male New Zeeland White rabbits weighing 4.5 kg of 9 - 15 months age were grouped, comprising of 8 and 7 animals in test group [Methadone + Omeprazole] and control [Methadone] respectively. The test group of rabbits were given omeprazole [60 umol/kg], suspended in normal saline orally by gavage for one week and methadone [10mg/kg] orally after one hour of omeprazole dose only on seventh day while the control group of rabbits were given physiological 0.9% of normal saline instead of omeprazole. Omeprazole delayed the oral absorption of methadone with average peak time of 2.4 hrs as compared to mean 1.38 hrs in controls [>0.05] and increased its AUC by 26%. The elimination half life and mean residence time were increased while total clearance reduced 29% in omeprazole treated rabbits [P < 0.01]. It is concluded that omeprazole slows elimination phase of methadone, so patients taking omeprazole for peptic ulcer, should be followed for any symptoms of methadone toxicity and the dose must be adjusted

Effect of colestipol on indomethacin pharmacokinetics in rabbits

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