ABSTRACT
OBJECTIVE: Methotrexate has been documented to accumulate in pleural effusions and ascitic fluid, resulting in severe local and systemic toxicity. In the following case report, we publish results of intraoperative measurements of methotrexate levels in serum and an ovarian cyst and attempt to determine if ovarian cysts similarly act as a depot for methotrexate. METHODS: After determining intraoperative measurements of serum and ovarian cystic levels of methotrexate, we compared demonstrated pharmacokinetics to those expected by using pharmacokinetic systems analysis software. RESULTS: Intraoperative measurement of methotrexate levels on day 3 of a 5-day methotrexate regimen revealed a serum methotrexate concentration of 1.6 x 10(-7) M and a concentration of 3.1 x 10(-7) M within the 166.4 ml ovarian cyst. CONCLUSIONS: The measured levels demonstrate that methotrexate is sequestered within an ovarian cyst resulting in higher local drug levels. Our pharmacokinetic analysis suggests that methotrexate doses less than 100 mg/m2 can be safely administered to patients with small ovarian cysts. However, computed simulations support the possibility of local and systemic toxicity arising from large ovarian cysts when using high doses of methotrexate.
