Effects of Allopurinol on Cytochrome P450 Isoforms in Rats

OBJECTIVE To study the change of the hepatic CYP450 activity following administration of allopurinol by Cocktail probe drugs in rats. METHODS The rats were randomly divided into two groups: rats were given allopurinol once daily orally for 14 days as the test group, another group received orally normal saline once daily as the blank control group. The plasma concentrations of Cocktail probe drugs were determined by HPLC-MS and their corresponding pharmacokinetic parameters were calculated. RESULTS AUC_(0-∞), C_max and t_1/2 of phenacetin notably increased and the CL decreased significantly after administered allopurinol for 14 consecutive days. But the pharmacokinetic parameters of tolbutamide, omeprazole and dextromethorphan had no statistical significance. CONCLUSION Allopurinol can inhibit CYP1A2 enzyme, but has little influence on metabolism of CYP2C9, CYP2C19 and CYP2D6 enzyme in rats.