Comparative bioavailability of alpha-methyldopa normal and film tablet formulations after single oral administration in healthy volunteers
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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.
KeywordsAlpha methyldopa pharmacokinetics bioavailability bioequivalence
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- 4.Skerjanec, A., Campbell, N.R.C., Robertson, S., Tam, Y.K. (1995): Pharmacokinetics and presystemic gut metabolism of methyldopa in healthy human subjects. Eur. J. Clin. Pharmacol, 35. 275–279.Google Scholar
- 7.Róna, K., Gachályi, B., Vereczkey, L., Nádas, B., Káldor, A. (1987): Comparative bioavailability study of two preparations of alpha-methyldopa after single oral doses. Int. J. Clin. Pharm. Ther. and Tox. 25: 515–517.Google Scholar
- 13.Drugs Directorate Guidelines (1992): Conduct and analysis of bioavailability and bioequivalence studies. Health and Welfare Canada, Ottawa.Google Scholar
- 14.Guidance, statistical process for bioequivalence studies using a standard two-treatment cross-over design. Food and Drug Administration (FDA), Division of Bioequivalence, Office of Generic Drugs, Rockville, MD, USA (1992).Google Scholar
- 15.Blume, H. H., Sievert, M. (1987): Qualitatsbeurteilung von wirkstoffgleichen Fertigarzneimitteln (Generik). Schriftereiche der Bayerishen Landesapotheker-kammer, Heft 36, München.Google Scholar
- 16.Good Clinical Practice (1994), Guideline for essencial documents for the conduct of a clinical trial, Comission of the European Communities, II/5058/94, Brusseles.Google Scholar
- 17.The OECD principles off Good Laboratory Practice (1992) OCDE/GD (92) 32, OECD, Paris.Google Scholar
- 18.Good Laboratory Practice (1993) Marcel Dekker, Inc., New York.Google Scholar
- 19.Shah, V. P., Midha, K. K., Dighe, S., McGilvery, I. J., Skelly, J. P., Yacobi, A., Layloft, T., Viswanathan, C. T., Cook, C. E., McDowall, R. D., Pittman, K. A., Spector, S., (1992): Analytical method validation, bioavailability, bioequivalence and pharmacokinetic studies. J. Pharm. Sci., 81, 309–312.CrossRefGoogle Scholar
- 22.Sváb, J. (1979): Multivariate methods in biometry (in Hung.). Mezôgazdasa-gi Kiadó, BudapestGoogle Scholar
- 24.Blume, H. H., Midha, K. K. (1995): Bio-International 2. Bioavailability bioequivalence and pharmacokinetic studies Medipharm Scientific Publishers, Stuttgart.Google Scholar