Comparative bioavailability of two oral formulations of clopidogrel: determination of clopidogrel and its carboxylic acid metabolite (SR26334) under fasting and fed conditions in healthy subjects.

Two randomized, single dose, 2-period, 2-sequence crossover studies were conducted to evaluate the comparative bioavailability of two clopidogrel formulations under fasting and fed conditions. Assessment of bioequivalence was based upon measurement of plasma concentrations of the parent drug, clopidogrel, and its major (inactive) metabolite, clopidogrel carboxylic acid, using improved methanol-free extraction. Bioequivalence of Krka's formulation to the innovator's formulation was demonstrated under both fasting and fed conditions on 205 volunteers. Confidence intervals for AUC0-t, AUC0-inf and Cmax of clopidogrel and its main metabolite were well within the acceptance range of 80.00 to 125.00 %. Food substantially increased the bioavailability of clopidogrel from both formulations, while no effect of food on the extent and rate of exposure to the metabolite was observed. The effect of food was comparable between the two formulations, as indicated by the same direction and rank of food impact on the bioavailability of both formulations.

Comparison of optic nerve head topography in healthy adults using a Heidelberg retina tomograph and retinal thickness analyzer.

PURPOSE: To compare optic nerve head topographies measured using a Heidelberg retina tomograph I (HRT) and a retinal thickness analyzer (RTA) and thereby to determine clinical agreement between the two devices. Also, to investigate the reproducibility of optic nerve head measurements using the HRT and RTA. METHODS: The study included 50 normal left eyes of 50 white adults. Ophthalmologic examination, keratometry, fundus photography, and examination with HRT and RTA were performed. To determine reproducibility, 10 volunteers had repeated examinations after a week. Mean (SD), median, and 5th and 95th percentiles were calculated for the HRT and RTA measurements and differences in measurements between HRT and RTA were tested for statistical significance. Clinical agreement was assessed with limits of agreement and reproducibility by a repeatability coefficient and intraclass correlation coefficient (ICC). RESULTS: Statistically significant differences (P < 0.05) between measurements by HRT and RTA were observed for all topographic parameters, except for rim area (P = 0.051) and height variation contour (P = 0.054). The limits of agreement between HRT and RTA were wide. The repeatability coefficient for HRT was good (< or =0.10) for all parameters, except for retinal nerve fibre layer (RNFL) cross-sectional area (0.28). The repeatability coefficient for RTA was >0.10 for cup area (0.15), rim area (0.19), maximum cup depth (0.13), height variation contour (0.11), and RNFL cross-sectional area (0.14). The ICC was good (> or =90%) for all parameters, except for mean RNFL thickness (89%) for HRT, and height variation contour (84%) for RTA. CONCLUSION: The observed differences within the limits of agreement were clinically important. Therefore, the two devices cannot be used interchangeably in clinical practice.