EFFECTS OF NOCLOPROST CLATHRATE ON ABSORPTION OF ACETYLSALICYLIC-ACID

The cytoprotective prostaglandin E(2) analog nocloprost clathrate (NOC LO) is tested as a prophylactic for gastrointestinal lesions of NSAID. The effects of 400 mu g NOCLO versus respective placebos with and wit hout equivalent amounts of beta-cyclodextrin on the pharmacokinetic be havior of acetylsalicylic acid (ASA), given 30 min after NOCLO, were s tudied in two single-blind, parallel-group trials. The trials were per formed in 15 male healthy volunteers (age 21 - 25 years, body weight 6 2 - 94 kg, body height 172 - 187 cm) with known N-acetylation and debr isoquine type hydroxylation phenotype. ASA, salicylic acid (SA), and s alicyluric acid (SU) in plasma and SA and SU in urine were measured by HPLC. NOCLO delayed the absorption of ASA (increased t(max), lower C- max) significantly in comparison with both placebos. AUC and clearance values were not changed by NOCLO premedication. There were neither di fferences between the two placebo groups nor between the two groups pr etreated with NOCLO with regard to any pharmacokinetic parameter. The changes in drug absorption are caused by the sum of those cytoprotecti ve effects of prostaglandin which are also determinants of drug absorp tion.