Comparative bioavailability of alpha-methyldopa normal and film tablet formulations after single oral administration in healthy volunteers.
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-infinity, AUC0-t, Cmax, Cmax/AUC0-infinity, t(max)) 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-infinity 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-infinity 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.
Róna
K
K
1st Department of Internal Medicine, Haynal Imre University of Health Sciences, Budapest, Hungary.
Ary
K
K
Renczes
G
G
Gachályi
B
B
Grézal
G Y
GY
Drabant
S
S
Klebovich
I
I
D000316:Adrenergic alpha-Agonists / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000328:Adult; D019540:Area Under Curve; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D006207:Half-Life; D006801:Humans; D008297:Male; D008750:Methyldopa / Q000008:administration & dosage / Q000493:pharmacokinetics*; D012995:Solubility; D013050:Spectrometry, Fluorescence; D013608:Tablets, Enteric-Coated; D013810:Therapeutic Equivalency
D000316:Adrenergic alpha-Agonists; D013608:Tablets, Enteric-Coated; D008750:Methyldopa