Bioequivalence assessment of two different tablet formulations of diltiazem after single and repeated doses in healthy subjects.
The study was performed on 14 healthy volunteers in order to compare the pharmacokinetics and hence assess the bioequivalence of two different tablet formulations of diltiazem administered orally. The study was carried out after single doses (60 mg) and repeated doses (60 mg three times a day for six days and 60 mg on the seventh day) according to a randomised, cross-over, open design. The pharmacokinetic parameters AUC0-infinity (ng h/ml), Tmax(h) and Cmax (ng/ml) were calculated for the two formulations after a single dose, while AUCt1-t2 (= AUC for a repetitive dose interval or dosing cycle, ng h/ml) and PTF (peak trough fluctuation) were calculated after repeated doses. The bioequivalence assessment was the shortest 90% confidence interval for the ratio (difference) of expected medians in the respective bioequivalence range (0.80-1.20). The results of this study show that, after either a single dose or repeated doses of test or reference formulations of diltiazem, the pharmacokinetics of the two formulations are similar. The ratios of AUC on day 1 (for single-dose treatment) and on day 7 (for repeated-dose treatment), and the corresponding 90% confidence intervals demonstrate bioequivalence between the two formulations of diltiazem within the accepted range of 0.80-1.20 (80-120%).
Loffreda
A
A
Pharmacology and Toxicology Institute, Medical School, Second University of Naples, Italy.
Matera
M G
MG
Vacca
C
C
Motola
G
G
De Santis
D
D
Ruggiero
A
A
Russo
F
F
Fici
F
F
Cantoni
V
V
Lampa
E
E
Rossi
F
F
D000328:Adult; D000704:Analysis of Variance; D001682:Biological Availability; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002626:Chemistry, Pharmaceutical; D018592:Cross-Over Studies; D004110:Diltiazem / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012372:ROC Curve; D018709:Statistics, Nonparametric; D013607:Tablets; D013810:Therapeutic Equivalency
D002121:Calcium Channel Blockers; D013607:Tablets; D004110:Diltiazem