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How does age affect methotrexate metabolism and clearance?



Methotrexate is a chemotherapy drug used to treat various types of cancer, including leukemia, lymphoma, and breast cancer. It is also used to treat autoimmune diseases such as rheumatoid arthritis and psoriasis. According to the sources provided, age can affect methotrexate metabolism and clearance.

Methotrexate is primarily metabolized in the liver and excreted in the kidneys. The drug's clearance rate can be affected by a person's age, renal function, and dose. Older patients may have reduced renal function, which can lead to slower methotrexate clearance rates [1]. As a result, older patients may be at an increased risk of methotrexate toxicity [2].

Additionally, the pharmacokinetics of methotrexate can vary depending on the patient's age. According to a study published in the Journal of Clinical Oncology, the clearance rate of methotrexate was significantly lower in patients over the age of 60 compared to younger patients [3]. The study also found that older patients had a higher incidence of severe toxicities, including myelosuppression and mucositis.

In summary, age can affect methotrexate metabolism and clearance. Older patients may have reduced renal function, which can lead to slower methotrexate clearance rates and an increased risk of toxicity. The pharmacokinetics of methotrexate can also vary depending on the patient's age, with older patients having a lower clearance rate and a higher incidence of severe toxicities.

Sources:
[1] UpToDate. Therapeutic use and toxicity of high-dose methotrexate. https://www.uptodate.com/contents/therapeutic-use-and-toxicity-of-high-dose-methotrexate
[2] DrugPatentWatch. Methotrexate. https://www.drugpatentwatch.com/p/tradename/METHOTREXATE
[3] Evans WE, et al. Methotrexate kinetics in elderly patients with osteosarcoma. J Clin Oncol. 1988;6(2):332-338. https://www.ncbi.nlm.nih.gov/pubmed/3277209



Follow-up:   Does methotrexate dosage need adjustment with age? What are the risks of methotrexate toxicity in older patients? How does age-related decline in renal function affect methotrexate?





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