Potential pharmacokinetic interactions of nocloprost clathrate with retarded theophylline and enteric coated diclofenac after single and repeated premedication in healthy volunteers.

Abstract

Pharmacokinetic interactions of cytoprotective prostaglandin E2 analog nocloprost clathrate with theophylline and diclofenac were studied in two placebo controlled, single-blind studies with parallel groups (n = 8) in healthy male volunteers (age 20-32 years, body weight 63-95 kg, body height 169-193 cm, Broca index 0.81-1.18). Nocloprost (200 micrograms) or placebo tablets were given twice daily (07:00 h a.m. and p.m.) for 8 days. Thirty min after the first administration on the first day (single) and 30 min after the last administration in the morning of the 8th day (repeated premedication), pharmacokinetic examinations with retarded theophylline capsules (250 mg) or enteric coated tablets of diclofenac (50 mg) were performed. Theophylline was measured using an HPLC- and diclofenac with a GC-method. Both single and repeated premedication with nocloprost did not significantly change any pharmacokinetic parameter of theophylline. There was only a tendency towards lower AUC of theophylline after both regimens of premedication. As far as diclofenac is concerned, single premedication increased significantly the rate of absorption and total body clearance but lowered the AUC of the NSAID. After repeated premedication, no parameter was significantly influenced. All pharmacokinetic changes observed are most likely without any clinical importance.