Effects of Food and Antacid on Oral Absorption of Misoprostol, A Synthetic Prostaglandin E1 Analog

Abstract

Misoprostol, a synthetic PGE₁ analog with mucosal protective and antisecretory properties, is rapidly and essentially completely metabolized to its active metabolite, misoprostol acid. Relative to fasting conditions administration of misoprostol with antacid resulted in reduced bioavailability, as manifested by lower AUC(0–4) values from (mean ± SD; n = 12) 417 ± 135 to 349 ± 108 pg · hr/ml (P < 0.05), without significant changes in the rate of absorption (t_max = 14 ± 8 [fasting] vs. 20 ± 14 min [with antacid]). The observed C_max values were also reduced (from 811 ± 317 to 689 ± 315 pg/ml), however, the difference was not statistically significant. Drug administration with a high-fat content meal resulted in a marked slowing in the absorption rate without a substantial decrease in the extent. Relative to fasting conditions food decreased misoprostol acid C_max from 811 ± 317 to 303 ± 176 pg/ml (P < 0.05) and increased t_max from 14 ± 8 to 64 ± 79 min (P < 0.05): the AUC changes remained statistically insignificant from 417 ± 135 to 373 ± 111 pg · hr/ml. Administration of misoprostol with food could potentially decrease the incidence of systemic side effects by reducing the early high peak plasma concentrations of misoprostol acid.