Modification de la pharmacocinétique du méthotrexate suite à l’administration d’amphotéricine B: à propos d’un cas

Methotrexate (MTX) is a cytotoxic drug widely used in oncohematology. It’s predominantly renally excreted. Renal dysfunction impairs plasma excretion of MTX and can lead to an increase in incidence of dose dependent side effects. Amphotericin B is an antifungal used in fungal infection, it can be nephrotoxic. We report modification of MTX pharmacokinetics in a patient with acute lymphoblastic leukaemia treated with MTX high-dose (MTX-HD) who experienced renal failure and rebound of MTX concentration after exposure to amphotericine B. The patient was treated with MTX-HD (5,160 mg/24 h) combined to rescue therapy including hydratation with sodium bicarbonate 0.9% fluids and administration of folinic acid. At H₂₄ of MTX-HD, he received for fungal infection amphotericine B (0.5 mg/kg the first day and 1 mg/kg the second day). The plasma MTX level fell to 0.29 μmol/l within 48 hours and then increase to 0.4 μmol/l at H₇₂, which is a potentially toxic level. The increase in the plasma MTX levels was associated with a renal function decrease. Amphotericine B was stopped, MTX levels and renal function were normalised after 24 hours (H₉₆). Administration of amphotericine B can induce renal impairment by tubular injury and renal vasoconstriction. Renal dysfunction explains modification of MTX pharmacokinetics and may expose to side effects of this cytotoxic drug.