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.
PIP: The pharmacokinetics and safety for early abortion of two intramuscular methotrexate doses were investigated in a randomized, controlled trial conducted at Magee Women's Hospital (Pittsburgh, Pennsylvania, US). The 20 study subjects, all with gestations under 50 days, were administered either 50 mg/sq. m (group 1, n = 10) or 60 mg/sq. m (group 2, n = 10). Methotrexate levels were measured serially for the first 24 hours and then every 24 hours for 7 days. On day 7, 800 mcg of misoprostol was administered vaginally and repeated 24 hours later if abortion did not occur. Complete abortion occurred in 9 women (90%) in group 1 and all 10 women in group 2. Success was immediate in 9 women in both groups. Methotrexate levels peaked within 1-2 hours and were nondetectable within 48 hours in all women in group 1 and within 72 hours in group 2. Both the maximum concentration of methotrexate and the area under the curve were significantly greater in group 2. Methotrexate clearance rates were 7.89 +or- 1.98 l/hr in group 1 and 5.55 +or- 0.83 l/hr in group 2. Methotrexate-related side effects included transient nausea, vomiting, diarrhea, headache, dizziness, and subjective fever or chills. Overall, these findings indicate both methotrexate regimens are safe treatment doses. A methotrexate dose of 50 mg/sq. m intramuscularly has the same clearance rates when administered during pregnancy as in a nonpregnant state and maximum concentrations do not reach sustained toxic levels.