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Comparative bioavailability of alpha-methyldopa normal and film tablet formulations after single oral administration in healthy volunteers

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Summary

In a single dose, randomized, cross-over study, with one week of wash-out period, the relative bioavailability of Dopegyt® tablets containing 250 mg alpha-methyldopa (AMD) and Presinol® film tablets with identical active ingredient content was examined in 24 healthy volunteers.

Since technologically two completely different preparations (a film-tablet and a non-film-tablet) having significantly different in vitro dissolution were to be compared, both preparations were compared to a third one, AMD solution (Dopegyt® solution) with 250 mg/50 ml concentration. Plasma concentrations of the drug were measured for 24 hours post-dose, applying HPLC with fluorometric detection. Pharmacokinetic parameters calculated from individual data (AUC0−∞, AUC0−t, Cmax, Cmax/AUC0−∞, tmax) were evaluated statistically. Wilcoxon’s nonparametric test and the four-way variance analysis could not detect any significant difference at the usual a=95% probability level in these pharmacokinetic parameters of the two tablet preparations. For AUC0−∞ at the 90% probability level, the confidence interval was 0.883–1.237 (with an estimated geometric mean of 1.045), for the test/reference ratio of Dopegyt® and Presinol® tablets, thus the two preparations proved to be bioequivalent. The relative bioavailability of Dopegyt® (test preparation) and Presinol® (reference preparation) calculated from the AUC0−∞ values was 116.7±56.7% that also confirmed bioequivalence. The results of all the applied statistical tests suggest that Dopegyt® and Presinol® can be considered as bioequivalent preparations.

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Authors and Affiliations

  1. 1st Department of Internal Medicine, Division of Clinical Pharmacology, Haynal Imre University of Health Sciences, Budapest, Hungary

    K. Róna, K. Ary, G. Renczes & B. Gachályi

  2. Department of Pharmacokinetics, EGIS Pharmaceuticals Ltd., P.O.Box 100, H-1475, Budapest, Hungary

    Gy. Grézal & I. Klebovich

  3. Medical Division, EGIS Pharmaceuticals Ltd., Budapest, Hungary

    S. Drabant

Authors
  1. K. Róna
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  2. K. Ary
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  3. G. Renczes
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  4. B. Gachályi
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  5. Gy. Grézal
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  6. S. Drabant
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  7. I. Klebovich
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Róna, K., Ary, K., Renczes, G. et al. Comparative bioavailability of alpha-methyldopa normal and film tablet formulations after single oral administration in healthy volunteers. Eur. J. Drug Metab. Pharmacokinet. 26, 25–30 (2001). https://doi.org/10.1007/BF03190372

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  • DOI: https://doi.org/10.1007/BF03190372

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