betadex and salicylurate

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.

Topics: Acetylation; Administration, Oral; Adult; Aspirin; beta-Cyclodextrins; Chromatography, High Pressure Liquid; Cyclodextrins; Drug Interactions; Hippurates; Humans; Intestinal Absorption; Male; Prostaglandins F, Synthetic; Salicylates; Salicylic Acid; Single-Blind Method; Vasodilator Agents

First- and second-order multivariate calibration of fluorescence data have been compared as regards the determination of anti-inflammatories and metabolites in the biological fluids serum and urine. The simultaneous resolution of naproxen-salicylic acid mixtures in serum and naproxen-salicylic acid-salicyluric acid mixtures in urine was accomplished and employed for a discussion of the relative advantages of the applied chemometric tools. The analysis of second-order fluorescence excitation-emission matrices was performed using iteratively reweighted generalized rank annihilation method (IRGRAM), parallel factor analysis (PARAFAC), and self-weighted alternating trilinear decomposition (SWATLD). The results were compared with first-order fluorescence emission data analyzed with partial least-squares regression (PLS). In all cases, the performance of the methods was improved through the formation of inclusion complexes of the analytes with beta-cyclodextrin. The concentration ranges in which the analytes could be determined were as follows: naproxen, 0-250 ng mL(-1) in serum and 0-200 ng mL(-1) in urine; salicylic acid, 0-500 ng mL(-1) in serum and 0-300 ng mL(-1) in urine, and salicyluric acid, 0-300 ng mL(-1) in urine.

Topics: Anti-Inflammatory Agents, Non-Steroidal; beta-Cyclodextrins; Calibration; Cyclodextrins; Hippurates; Humans; Least-Squares Analysis; Multivariate Analysis; Naproxen; Salicylic Acid; Spectrometry, Fluorescence