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