Differential effects of misoprostol and ranitidine on the pharmacokinetics of diclofenac and gastrointestinal symptoms.
1. The effects of oral misoprostol (800 microg 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 Cmax 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).
Dammann
H G
HG
Krankenhaus Bethanien, Hamburg, Germany.
Simon-Schultz
J
J
Steinhoff
I
I
Damaschke
A
A
Schmoldt
A
A
Sallowsky
E
E
D000284:Administration, Oral; D000328:Adult; D000704:Analysis of Variance; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000097:blood / Q000493:pharmacokinetics*; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D003672:Defecation / Q000187:drug effects; D004008:Diclofenac / Q000097:blood / Q000493:pharmacokinetics*; D004338:Drug Combinations; D004347:Drug Interactions; D005243:Feces; D006801:Humans; D008297:Male; D016595:Misoprostol / Q000494:pharmacology*; D011899:Ranitidine / Q000494:pharmacology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000897:Anti-Ulcer Agents; D004338:Drug Combinations; D016595:Misoprostol; D004008:Diclofenac; D011899:Ranitidine