The effects of misoprostol (200 micrograms as a single dose or q.i.d. as a multiple dose) on the pharmacokinetics of indomethacin (100 mg single-dose administration or 50 mg t.i.d. multiple-dose administration) were studied in 16 healthy human volunteers under single-dose and steady-state conditions in a randomized, double-blind, placebo-controlled, balanced three-period study design. The overall absorption as shown by the values for area under the concentration curve of indomethacin was unaffected by concurrent administration of misoprostol. However, misoprostol did significantly enhance the steady-state maximum concentration of indomethacin by 32%. Thus misoprostol does not interfere with the absorption of indomethacin despite the known inhibitory effects of this protaglandin analog on acid secretion.