Methotrexate pharmacokinetics and effects in women receiving methotrexate 50 mg and 60 mg per square meter for early abortion.

OBJECTIVE

Our goal was to evaluate the pharmacokinetics and safety of methotrexate in doses of 50 mg/m2 and 60 mg/m2 in regimens for early abortion.

STUDY DESIGN

A randomized controlled trial was performed in women requesting an abortion at < or = 49 days' gestation. Twenty women were treated with intramuscular methotrexate 50 mg/m2 (group 1) or 60 mg/m2 (group 2). Methotrexate levels were determined serially for the first 24 hours, then every 24 hours for 7 days. On the seventh day misoprostol 800 microg was administered vaginally. The misoprostol dose was repeated 24 hours later if abortion did not occur.

RESULTS

Complete abortion occurred in 9 of 10 (90%, 95% confidence interval 56% to 100%) patients in group 1 and all 10 (100%, 95% confidence interval 69% to 100%; p = 0.99) in group 2. Methotrexate levels peaked within 1 to 2 hours and were nondetectable within 48 hours in all patients in group 1 and 72 hours in group 2. Both the maximum concentration of methotrexate and the area under the curve were significantly greater for group 2. Methotrexate clearance rates were 7.89 +/- 1.98 L/hr and 5.55 +/- 0.83 L/hr (p = 0.003), respectively.

CONCLUSIONS

The serum levels of intramuscular methotrexate with 50 mg/m2 and 60 mg/m2 regimens indicate that these are safe treatment doses. Methotrexate 50 mg/m2 intramuscularly has the same clearance rates when administered during pregnancy as in a nonpregnant state, and maximum concentrations do not reach sustained toxic levels.