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/m(2) and 60 mg/m(2) in regimens for ea rly abortion. STUDY DESIGN: A randomized controlled trial was performe d in women requesting an abortion at less than or equal to 49 days' ge station. Twenty women were treated with intramuscular methotrexate 50 mg/m(2) (group 1) or 60 mg/m(2) (group 2). Methotrexate levels were de termined serially for the first 24 hours, then every 24 hours for 7 da ys. On the seventh day misoprostol 800 mu g 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% confi dence 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 le vels 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 signif icantly 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. CONCLUSI ONS: The serum levels of intramuscular methotrexate with 50 mg/m(2) an d 60 mg/m(2) regimens indicate that these are safe treatment doses. Me thotrexate 50 mg/m(2) intramuscularly has the same clearance rates whe n administered during pregnancy as in a nonpregnant state, and maximum concentrations do not reach sustained toxic levels.