Methotrexate sequestration in an ovarian cyst

Objective. Methotrexate has been documented to accumulate in pleural effusi ons and ascitic fluid, resulting in severe local and systemic toxicity. In the following case report, we publish results of intraoperative measurement s of methotrexate levels in serum and an ovarian cyst and attempt to determ ine 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 t o 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 ovari an cyst. Conclusions. The measured levels demonstrate that methotrexate is sequester ed within an ovarian cyst resulting in higher local drug levels. Our pharma cokinetic analysis suggests that methotrexate doses less than 100 mg/m(2) c an be safely administered to patients with small ovarian cysts. However, co mputed simulations support the possibility of local and systemic toxicity a rising from large ovarian cysts when using high doses of methotrexate. (C) 1999 Academic Press.