Is there any risk of a metabolic interaction between colchicine and omeprazole? Is there any differ

Fråga: Is there any risk of a metabolic interaction between colchicine and omeprazole? Is there any difference between omeprazole and esomeprazole in this respect? A patient with Bechet´s disease who is taking colchicine, 0.5 mg 3 times a day, is now also prescribed omeprazole 20 mg per day. In addition to that, she is also taking 5 mg of prednisolone daily.

Sammanfattning: No interactions between colchicine and omeprazole are published in the literature and are not to be expected from a clinical point of view.

Svar: No reports of interactions between colchicine and omeprazole have been found in Drugline, Medline or common pharmacological literature.

It has been shown that both P-glycoprotein (Pgp) and cytochrome P-450 3A4 (CYP3A4) are involved in colchicine elimination (1). The production of colchicine´s two main metabolites, 3-demethylcolchicine (3DMC) and 2-demethylcolchicine (2DMC), is mediated by CYP3A4 activity (2). Around 5-20 % of colchicine is excreted unchanged in the urine (1). The co-administration of colchicine with potent inhibitors or substrates of CYP3A4 may inhibit its elimination and result in increased plasma concentration and toxic levels of colchicine (2).

Omeprazole is mainly metabolised in the liver by CYP2C19, which form a sulfone metabolite, and CYP3A4, which form 5-O-desmethyl- and hydroxymetabolites (3,4). Its metabolism is, however, more dependent of the CYP2C19 activity than on the CYP3A4 activity (4). CYP2C19 is an enzyme subject to genetic polymorphism, and poor metabolisers (3 % of Caucasians and 10-20 % of Orientals) will have much higher concentrations of omeprazole than normal metabolisers. In poor metabolisers the metabolism will be more dependent of CYP3A4 and this might be a target for drug interactions (3). It has also been found that the metabolism of omeprazole is stereo selective and CYP2C19 is responsible for about 70 percent of the metabolism of S-omeprazole and about 90 percent of R-omeprazole (4). Omeprazole is a known inhibitor of CYP2C19 but not of CYP3A4 and does not seem to induce the activity of the latter (3,5).

Esomeprazole, the S-enantiomer of omeprazole, has the same metabolic pathways as the racemic mixture, omeprazole. The substance does not interact with CYP3A4 substrates and seem to have similar interaction potentials as omeprazole (6).

Prednisolone is thought to be partly metabolised by CYP3A4 (7). No case reports of an interaction between colchicine and prednisolone have been found in literature.

Theoretically colchicine and omeprazole could interact by competitive inhibition, but since the metabolism of omeprazole is mainly going through the CYP2C19 pathway an interaction seems unlikely. Since prednisolone is metabolised by the same enzyme as colchicine an interaction between these two is theoretically possible.