Effect of colchicine on rat hepatic cytochrome P450 enzymes by cocktail probe drugs.

[familial mediterranean fever]

Colchicine (COL ), an alkaloid derived from plants , has been used to treat gout , pseudogout and familial Mediterranean fever for several decades . The purpose of this study was to investigate the in vivo effect of COL on rat cytochrome P 450 enzymes (CYP 1 A 2 , CYP 2 C 9 , CYP 2 C 19 and CYP 2 D 6 ) to assess its potential to interact with co -administered drugs . This was a randomized , double -blind , two -way crossover study with a 4 -week washout period between the phases . Rats received COL via an irrigation stomach needle at a dose of 0 .4 mg /kg once daily for consecutive 10 days . On the eleventh day , a cocktail solution at a dose of 4 ml /kg , which contained phenacetin (15 .0 mg /kg ), tolbutamide (3 .0 mg /kg ), omeprazole (15 .0 mg /kg ) and dextromethorphan (15 .0 mg /kg ), was oral administered to all rats . Then 0 .3 ml blood samples were collected at a set of time-points . The plasma concentrations of probe drugs were simultaneously determined by HPLC-MS /MS . Pharmacokinetic parameters simulated by DAS software were used for the evaluation of COL on the activities of rat CYP 1 A 2 , CYP 2 C 9 , CYP 2 C 19 and CYP 2 D 6 enzymes . Our study showed that COL administration induced CYP 2 C 9 activity , causing a significant decrease in AUC (0 -infinity ) (P < 0 .01 ) and t 1 /2 (P < 0 .05 ) of tolbutamide , and a distinct increase in CL (P <0 .01 ). Many pharmacokinetic parameters of dextromethorphan in COL-treated rats were affected significantly , which indicated that the metabolism of dextromethorphan in these treatment groups was evidently slowed down . However , there was no significant influence of pharmacokinetic parameters of phenacetin and omeprazole in COL-treated rats . The results from the present in vivo study suggested that COL showed no effects on rat CYP 1 A 2 and CYP 2 C 19 , however , it demonstrated potential inductive effects on CYP 2 C 9 and inhibitory effects on CYP 2 D 6 . Therefore , caution is needed when COL is co -administered with drugs metabolized by CYP 2 C 9 or CYP 2 D 6 , which may result in altered plasma concentrations of these drugs and relevant drug-drug interactions .

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familial mediterranean fever

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