Methotrexate pneumonitis induced by intrathecal methotrexate therapy: a case report with pharmacokinetic data

A patient with adenocarcinoma of the breast metastatic to the leptomeninges was treated with 10 doses of intrathecal methotrexate (MTX) administered at intervals of 2 days. Following these treatments she developed fever, hypoxemia, and bilateral pulmonary infiltrates without documented pulmonary infection. Autopsy findings were consistent with the pneumonitis that has been associated with intermittent oral, intramuscular, and intravenous MTX therapy. It is suggested that this patient's pulmonary process represented MTX pneumonitis following intrathecal MTX. Cerebrospinal fluid and serum MTX concentrations determined retrospectively on frozen samples reflect an atypically rapid transport of MTX from this patient's cerebrospinal fluid to a slowly decaying systemic pool. Because of this, serum MTX levels probably exceeded 10-8M during the entire 20-day course of therapy, thus exposing the pulmonary parenchyma to significant drug concentrations for a prolonged interval. It is suggested that these unfavorable pharmacokinetics may have contributed to this patient's susceptibility to MTX pneumonitis.