Which drug increases methotrexate concentration?

Which drug increases methotrexate concentration?

• A. Acetaminophen
• B. Furosemide
• C. Phenytoin
• D. Lisinopril

Answer: (C)

Drug interactions that alter methotrexate exposure often involve changes in protein binding or renal clearance. Methotrexate is partly bound to serum proteins, and when a drug that is itself highly protein-bound is present, it can displace methotrexate from albumin. This raises the free (unbound) fraction of methotrexate in the blood, leading to higher active concentrations and an increased risk of toxicity. Phenytoin has strong protein binding and can compete for binding sites on albumin, effectively releasing more methotrexate into the free pool. This makes it the drug most likely among the options to raise methotrexate concentration and toxicity risk. Acetaminophen doesn’t significantly alter methotrexate protein binding. Furosemide can affect renal clearance indirectly through volume status or renal function, but it isn’t a primary protein-binding displacement issue. Lisinopril’s effect is more related to renal handling than direct displacement of protein-bound methotrexate.

Drug interactions that alter methotrexate exposure often involve changes in protein binding or renal clearance. Methotrexate is partly bound to serum proteins, and when a drug that is itself highly protein-bound is present, it can displace methotrexate from albumin. This raises the free (unbound) fraction of methotrexate in the blood, leading to higher active concentrations and an increased risk of toxicity.

Phenytoin has strong protein binding and can compete for binding sites on albumin, effectively releasing more methotrexate into the free pool. This makes it the drug most likely among the options to raise methotrexate concentration and toxicity risk.

Acetaminophen doesn’t significantly alter methotrexate protein binding. Furosemide can affect renal clearance indirectly through volume status or renal function, but it isn’t a primary protein-binding displacement issue. Lisinopril’s effect is more related to renal handling than direct displacement of protein-bound methotrexate.