Effect of oral cholestyramine on the elimination of high-dose methotrexate

Abstract

The anion exchange resin cholestyramine binds methotrexate (MTX) effectively in vitro. The binding capacity exceeds that of activated charcoal by a factor of 5.4. On two patients undergoing high-dose MTX therapy it is also shown that cholestyramine binds MTX in vivo. This leads to an enhanced non-renal excretion of MTX. Therefore, cholestyramine may be of clinical value in patients who develop renal function impairment whilst undergoing MTX therapy.

Successful rescue by oral cholestyramine of a patient with methotrexate nephrotoxicity: Nonrenal excretion of serum methotrexate

“…This treatment is therefore a simple, useful merans of controlling serum MTX under nephrotoxic conditions. As was done here, administration of high dose leucovorin also plays an important role in achieving successful rescue [7]. Clearly, regular measurement of serum MTX to concentrations is very important to prevent lethal side effects and measures allow strenuous rescue to be commenced as soon as toxic conditions become manifest.…”

“…Enterohepatic circulation is therefore a second elimination pathway [5,7]. Cholestyramine is an anion exchange resin that binds MTX in vitro [7], and when given orally also in the enterohepatic circulation, thus facilitating MTX excretion [7].…”

In Vitro Study of the Adsorption Characteristics of Drugs

“…The serum MTX concentration 24 h after the MTX infusion was about 50% of the concentration measured after the first course of MTX given without cholestyramine. 6) Additionally, it was also reported that cholestyramine and colestimide had high adsorption capacities for MTX in an in vitro study. 7,8) In our study, medicinal carbon, cholestyramine and colestimide showed high adsorptions for MTX, in addition, the carbon spheres showed a slow but high adsorption manner.…”

Effect of Oral Colestimide on the Elimination of High-dose Methotrexate in Patients With Primary Central Nervous System Lymphoma-Two Case Reports-

“…9) This may be due to adsorption of biliary excreted MTX which is consequently not reabsorbed enterally. Oral cholestyramine facilitates MTX excretion in the enterohepatic circulation 8,14) without affecting the serum MTX level at 24 hours after infusion, which may reflect the renal elimination of the drug 8) and suggests that cholestyramine may improve the total body clearance of MTX by enhancing extrarenal excretion.…”

“…Therefore, cholestyramine could accelerate MTX elimination in patients experiencing toxicity associated with high-dose MTX therapy by binding MTX in the gut and interrupting the enterohepatic circulation. 8) Colestimide, a new type of anion-exchange resin, is reported to effectively absorb MTX. 10) We treated two patients with high-dose MTX administration for primary CNS lymphoma which resulted in the delayed elimination of MTX.…”