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Effects of nocloprost clathrate on absorption of acetylsalicylic acid.

Abstract
The cytoprotective prostaglandin E2 analog nocloprost clathrate (NOCLO) is tested as a prophylactic for gastrointestinal lesions of NSAID. The effects of 400 micrograms NOCLO versus respective placebos with and without equivalent amounts of beta-cyclodextrin on the pharmacokinetic behavior of acetylsalicylic acid (ASA), given 30 min after NOCLO, were studied in two single-blind, parallel-group trials. The trials were performed in 15 male healthy volunteers (age 21-25 years, body weight 62-94 kg, body height 172-187 cm) with known N-acetylation and debrisoquine type hydroxylation phenotype. ASA, salicylic acid (SA), and salicyluric acid (SU) in plasma and SA and SU in urine were measured by HPLC. NOCLO delayed the absorption of ASA (increased tmax, lower Cmax) significantly in comparison with both placebos. AUC and clearance values were not changed by NOCLO premedication. There were neither differences between the two placebo groups nor between the two groups pretreated with NOCLO with regard to any pharmacokinetic parameter. The changes in drug absorption are caused by the sum of those cytoprotective effects of prostaglandin which are also determinants of drug absorption.
AuthorsW Siegmund, M Zschiesche, G Franke, I Amon
JournalInternational journal of clinical pharmacology and therapeutics (Int J Clin Pharmacol Ther) Vol. 32 Issue 1 Pg. 51-7 (Jan 1994) ISSN: 0946-1965 [Print] Germany
PMID8199752 (Publication Type: Clinical Trial, Clinical Trial, Phase I, Clinical Trial, Phase II, Comparative Study, Controlled Clinical Trial, Journal Article)
Chemical References
  • Cyclodextrins
  • Hippurates
  • Prostaglandins F, Synthetic
  • Salicylates
  • Vasodilator Agents
  • beta-Cyclodextrins
  • salicylurate
  • nocloprost
  • betadex
  • Salicylic Acid
  • Aspirin
Topics
  • Acetylation
  • Administration, Oral
  • Adult
  • Aspirin (blood, metabolism, pharmacokinetics)
  • Chromatography, High Pressure Liquid
  • Cyclodextrins (pharmacology)
  • Drug Interactions
  • Hippurates (blood)
  • Humans
  • Intestinal Absorption (drug effects)
  • Male
  • Prostaglandins F, Synthetic (pharmacology)
  • Salicylates (urine)
  • Salicylic Acid
  • Single-Blind Method
  • Vasodilator Agents (pharmacology)
  • beta-Cyclodextrins

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