Misoprostol versus methylergometrine: pharmacokinetics in human milk

OBJECTIVE: The purpose of this study to compare breast milk pharmacokinetics between misoprostol 200 mug and methylergometrine 250 mug after single oral dosing in women who require postpartum uterotonic therapy. STUDY DESIGN: Open prospective randomized phase I study measuring misoprostol and methylergometrine on postpartum days 3 to 6 in milk 0.5, 1, 2, 3, 4, and 5 hours postdose, and in maternal serum at 0.5 and 1 hours (misoprostol) and 1 and 2 hours (methylergometrine) in 10 lactating women per group. RESULTS: Milk misoprostol levels rose and declined rapidly, which gave a milk elimination half-life of less than one half that of methylergometrine (mean +/- SE, 1.1 +/- 0.3 hours median, 0.6 hours] vs 2.33 +/- 0.3 hours median, 1.9 hours]; P = .003). Milk/plasma ratios for misoprostol were one third of those for methylergometrine at 1 hour ( P < .0001) and 2 hours ( P < .0015). CONCLUSION: Misoprostol warrants further investigation as an alternative to postpartum methylergometrine because it enters and leaves breast milk at twice the rate, with one third of the milk/plasma ratio, which significantly lowers infant exposure and facilitates a timed dosing regimen.