Bioequivalence study of two minocycline capsule formulations in healthy volunteers.
The bioequivalence of two capsule formulations containing 100 mg minocycline was assessed in 12 healthy adult male and female volunteers in a crossover, randomized, single-blind study. The participating volunteers were required to fast overnight and in the next morning and were given orally one capsule of the test drug (Acnez) or one capsule of the reference drug. Blood samples were drawn immediately before taking the drug (control), and at 0.33, 0.67, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, and 60 h after drug administration. One week after the first drug administration (washout period), the procedure was repeated using the alternate drug. Plasma concentrations of the drug were determined by high performance liquid chromatography method with ultraviolet detection (HPLC-UV). The pharmacokinetic parameters assessed in this study were area under the plasma concentration-time curve from time zero to 60 h (AUC(t)), area under the plasma concentration-time curve from time zero to infinity (AUC(inf)), the peak plasma concentration of the drug (C(max)), time needed to achieve the peak plasma concentration (t(max)), and the elimination half life (t1/2). The mean AUC(t), AUC(inf), C(max), and t were 18038.55 ng x h x mL(-1), 19648.21 ng x h x mL(-1), 1076.01 ng x mL(-1), and 17.33 h, respectively, for the test drug and 17979.43 ng x h x mL(-1), 19639.78 ng x h x mL(-1), 1095.97 ng x mL(-1), and 16.44 h, respectively, for the reference drug. The median (range) of t(max) of the test drug and reference drug were 2.0 (1.0-4.0) h and 2.0 (0.67-4.0) h, respectively. The geometric mean ratios of the test drug/the reference drug for AUC(t), AUC(inf), and C(max) were 98.27% 98.30%, and 97.31%, respectively. The 90% confidence intervals (CIs) were 89.26-108.19% for AUC(t), 89.95-107.41% for AUC(inf), and 89.55-105.73% for C(max). Using Wilcoxon matched-pairs test on the original data, there was no statistically significant difference found between the test and the reference drug products for t(max), values. It can be concluded that the two minocycline capsules (test drug and reference drug) are 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
Purnomo
Asri
A
Deniati
Siti Hawa
SH
Yunaidi
Danang Agung
DA
Handayani
Lucia Rat
LR
Harinato
Gunawan
G
Santoso
Iwan Dwi
ID
D000328:Adult; D000465:Algorithms; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002626:Chemistry, Pharmaceutical; D018592:Cross-Over Studies; D005260:Female; D006801:Humans; D008297:Male; D008911:Minocycline / Q000008:administration & dosage / Q000493:pharmacokinetics*; D016037:Single-Blind Method; D013810:Therapeutic Equivalency; D055815:Young Adult
D000900:Anti-Bacterial Agents; D008911:Minocycline