Comparative bioavailability of two estazolam tablet formulations in Indonesian healthy volunteers.
OBJECTIVE
To compare the bioavailability of two estazolam (CAS 29975-16-4) tablet formulations (Estalin 2 mg tablets as test formulation and 2 mg tablets of the originator product as reference formulation).


METHODS
The study was conducted according to an open label, randomized two-way cross-over design with a two-week washout period. Twenty-four subjects received each of the two estazolam formulations. Blood samples for pharmacokinetic profiling were taken up to 72 h after drug administration in fasting condition. Plasma concentrations of estazolam were determined with a validated HPLC method with ultraviolet detection. Pharmacokinetic parameters were calculated from observed plasma concentration-time profiles.


RESULTS
The mean AUC(0-t), AUC(0-infinity) and Cmax were 2581.38 ng x h/mL, 2934.37 ng x h/mL and 95.25 ng/mL, respectively for the test formulation and 2835.75 ng x h/ mL, 3207.73 ng x h/mL and 99.32 ng/mL, respectively, for the reference formulation. The median Tmax for both formulations was 1 h. The point estimates and 90% confidence Intervals for AUC(0-t), AUC(0-infinity) and Cmax were 91.03% (87.48-94.72%), 91.48% (86.67-96.55%) and 95.90% (92.60-99.31%) respectively, satisfying the bloequivalence criteria of the European Committee for Proprietary Medicinal Products and the US Food and Drug Administration guidelines.


CONCLUSIONS
These results indicate that two formulations of estazolam are bioequivalent and, thus, may be prescribed interchangeably.
Harahap
Yahdiana
Y
Department of Pharmacy, Faculty of Mathematic and Science, University of Indonesia, Depok, Indonesia.
Sasongko
Lucy
L
Prasaja
Budi
B
Indriati
Ega
E
Lusthom
Windy
W
Lipin
D000293:Adolescent; D000328:Adult; D014151:Anti-Anxiety Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D004949:Estazolam / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D007214:Indonesia; D008297:Male; D013607:Tablets; D013810:Therapeutic Equivalency; D055815:Young Adult
D014151:Anti-Anxiety Agents; D013607:Tablets; D004949:Estazolam