Hg. Dammann et al., DIFFERENTIAL-EFFECTS OF MISOPROSTOL AND RANITIDINE ON THE PHARMACOKINETICS OF DICLOFENAC AND GASTROINTESTINAL SYMPTOMS, British journal of clinical pharmacology, 36(4), 1993, pp. 345-349
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 dos
e of diclofenac was given orally on days 1 and 8, and plasma diclofena
c concentrations were measured by h.p.l.c. over 24 h. 3 Misoprostol ca
used a non-significant 19% increase in the mean C(max) value of diclof
enac on both days 1 and 8. After 8 days of dosing with misoprostol the
re was a significant (P = 0.04) 20% decrease in the AUC of diclofenac.
4 Ranitidine had no statistically significant effects on the pharmaco
kinetics of diclofenac. 5 Co-administration of misoprostol and diclofe
nac was associated with a higher frequency and severity of gastrointes
tinal symptoms and frequency of bowel opening, and a decrease in faeca
l consistency when compared with either placebo or ranitidine plus dic
lofenac (P < 0.01).