Bioequivalence study of two azithromycin formulations in healthy subjects.
The study was conducted to find out whether the bioavailability of a 500 mg azithromycin (CAS 83905-01-5) tablet (Zycin, test) was equivalent to that of a reference formulation. The pharmacokinetic parameters assessed in this study were the area under the plasma concentration-time curve from time zero to 120 h (AUCt), area under the plasma concentration-time curve from time zero to infinity (AUCinf), the peak plasma concentration of the drug (Cmax), time needed to achieve the peak plasma concentration (tmax), and the elimination half-life (t1/2). This was a randomized, single blind, two-period, cross-over study which included 18 healthy adult male and female subjects under fasting conditions. In each of the two study periods (separated by a washout of two weeks) a single dose of test or reference drug was administered. Blood samples were taken up to 120 h post dose, the plasma was separated and the concentrations of azithromycin were determined by a LC-MS/MS method. In this study, the mean AUCt, AUCinf, Cmax, and t1/2 of azithromycin from the test drug were 4967.49 ng x h x mL(-1), 5871.74 ng x h x mL(-1), 412.14 ng/mL, and 51.32 h, respectively. The mean AUCt, AUCinf, Cmax, and t1/2 of azithromycin from the reference drug were 4276.75 ng x h x mL(-1), 5578.12 ng x h x mL(-1), 419.89 ng/mL, and 51.23 h, respectively. The median tmax of he test drug and reference drug were 3.0 h and 2.0 h, respectively. The geometric mean ratios (90% CI) of the test drug/reference drug for azithromycin were 101.56% (86.61-119.08%) for AUCt, 101.27% (84.97-120.70%) for AUCinf, and 97.78% (84.50-113.16%) for Cmax. Based on this study, it was concluded that the two azithromycin tablets (test and reference drug) were bioequivalent in terms of the rate and extent of absorption.
Setiawati
Effi
E
PT Equilab International, Bioavailability and Bioequivalence Laboratory, Jakarta, Indonesia. effi@equilab-int.com
Deniati
Siti Hawa
SH
Yunaidi
Danang Agung
DA
Handayani
Lucia Rat
LR
Harinanto
Gunawan
G
Santoso
Iwan Dwi
ID
Sari
Asriningtyas Purnomo
AP
Rimainar
Atika
A
D000293:Adolescent; D000328:Adult; D000465:Algorithms; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019540:Area Under Curve; D017963:Azithromycin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D021241:Spectrometry, Mass, Electrospray Ionization; D053719:Tandem Mass Spectrometry; D013810:Therapeutic Equivalency; D055815:Young Adult
D000900:Anti-Bacterial Agents; D017963:Azithromycin