Adsorption of methotrexate and calcium leucovorin onto cholestyramine in vitro

Abstract

Methotrexate (MTX), an antimetabolite of folic acid, is a drug widely used in the treatment of different types of cancer. When high doses are administered, it is necessary to interrupt its action by administering calcium leucovorin (CaL). The main pathway of MTX and CaL elimination in humans occurs through the kidney, but about 10% is excreted in the faeces via the bile. Drugs, foods and sorbents in intestinal lumen modify MTX and CaL reabsorption. Individual and simultaneous studies on the adsorption of MTX and CaL from aqueous phosphate buffer by cholestyramine were carried out in order to calculate the adsorption process of MTX and CaL to cholestyramine, and to characterize the influence of CaL in the adsorption of MTX to cholestyramine and vice versa. The Langmuir binding isotherms determined in buffer solutions at pH 6 indicated a greater (12.58%) adsorption capacity of cholestyramine (1.43 mmol of drug/g of resin) than at pH 7 (1.25 mmol of drug/g of cholestyramine). The affinity constant of MTX to cholestyramine was a 45.27% higher (6.67 mM(-1)) than the affinity constant of CaL to the resin (3.65 mM(-1)). Results from simultaneous assays indicate that a displacement of the MTX bound to cholestyramine by CaL is not foreseeable. The results suggest that cholestyramine may be a potentially useful adjunctive therapy in the treatment of an overdose of MTX. Consequently, cholestyramine may be of clinical value in patients who develop early renal function impairment whilst undergoing MTX therapy.