Voriconazole injection may induce delayed methotrexate excretion: a case report and experimental study

Area of Science:

• Pharmacology
• Toxicology
• Nephrology

Background:

• A pediatric patient on high-dose methotrexate (HD-MTX) therapy experienced delayed MTX excretion after switching from oral to intravenous voriconazole.
• Intravenous voriconazole contains sulfobutylether-β-cyclodextrin (SBECD), an anionic excipient, unlike the oral formulation.

Purpose of the Study:

• To investigate the hypothesis that SBECD inhibits the renal excretion of anionic compounds.
• To evaluate the impact of SBECD on the renal clearance of phenolsulfonphthalein (PSP), an anionic drug eliminated via organic anion transporters.

Main Methods:

• Rats were administered intravenous PSP at 2.5 and 25 mg/kg, with or without SBECD pretreatment (320 mg/kg).
• Renal excretion and plasma concentrations of PSP were measured in control and SBECD-treated groups.

Main Results:

• SBECD did not significantly affect PSP elimination at a low dose (2.5 mg/kg).
• At a higher dose (25 mg/kg), SBECD significantly delayed PSP elimination, reducing its clearance from 9.71 ± 1.65 mL/min/kg to 4.13 ± 0.76 mL/min/kg (p < 0.05).
• These findings suggest SBECD partially inhibits the renal excretion of anionic drugs.

Conclusions:

• SBECD may contribute to delayed MTX elimination in patients receiving HD-MTX therapy.
• Avoiding SBECD-containing formulations is advisable for patients undergoing HD-MTX treatment.
• Further studies are warranted to confirm SBECD's inhibitory effect on MTX renal excretion, particularly in high-dose regimens.