DIFFERENTIAL-EFFECTS OF MISOPROSTOL AND RANITIDINE ON THE PHARMACOKINETICS OF DICLOFENAC AND GASTROINTESTINAL SYMPTOMS

1 The effects of oral misoprostol (800 mug day-1) and ranitidine (300 mg day-1) on the pharmacokinetics of diclofenac (100 mg) were assessed in a three-way randomized crossover study in 18 healthy male subjects. 2 Subjects were studied over three 8 day periods, during which they received twice-daily placebo, misoprostol, or ranitidine. A single dose of diclofenac was given orally on days 1 and 8, and plasma diclofenac concentrations were measured by h.p.l.c. over 24 h. 3 Misoprostol caused a non-significant 19% increase in the mean C(max) value of diclofenac on both days 1 and 8. After 8 days of dosing with misoprostol there was a significant (P = 0.04) 20% decrease in the AUC of diclofenac. 4 Ranitidine had no statistically significant effects on the pharmacokinetics of diclofenac. 5 Co-administration of misoprostol and diclofenac was associated with a higher frequency and severity of gastrointestinal symptoms and frequency of bowel opening, and a decrease in faecal consistency when compared with either placebo or ranitidine plus diclofenac (P < 0.01).