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 ≤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 μg 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.