Pharmacokinetics and Bioequivalence Studies of Galantamine Hydrobromide Dispersible Tablet in Healthy Male Chinese Volunteers

• Published in: Drug development and industrial pharmacy Vol. 33; no. 3; pp. 335 - 340
• Main Authors: Zhang, Li-jun, Fang, Xiao-ling, Li, Xue-ning, Wang, Qing-song, Han, Li-mei, Zhang, Zhi-wen, Sha, Xian-yi
• Format: Journal Article
• Language: English
• Published: Colchester Informa UK Ltd 01.03.2007; Taylor & Francis
• Subjects: Adult; Area Under Curve; Bioequivalence; Biological and medical sciences; China; Cholinesterase Inhibitors - blood; Cholinesterase Inhibitors - pharmacokinetics; Chromatography, High Pressure Liquid; Cross-Over Studies; Galantamine; Galantamine - blood; Galantamine - pharmacokinetics; General pharmacology; High-performance liquid chromatography; Humans; Male; Medical sciences; Pharmaceutical technology. Pharmaceutical industry; Pharmacokinetics; Pharmacology. Drug treatments; Tablets; Therapeutic Equivalency; Asia; China; Human; Pharmaceutical technology; Bioequivalence; Galantamine; Healthy subject; Enzyme; Benzazepine derivatives; Enzyme inhibitor; HPLC chromatography; Esterases; Antialzheimer agent; Acetylcholinesterase; High-performance liquid chromatography; Carboxylic ester hydrolases; Parasympathomimetic; Alkaloid; Dosage form; Hydrolases; Tablet; Anticholinesterase agent; Pharmacokinetics
• ISSN: 0363-9045; 1520-5762
• DOI: 10.1080/03639040600868011

ABSTRACT A randomized, two-way, crossover study was conducted in 18 healthy male Chinese volunteers to compare pharmacokinetics profiles of galantamine hydrobromide dispersible tablet with that of conventional tablet. A single oral dose of 10 mg galantamine was administrated to each volunteer. Plasma concentrations of galantamine were determined by a validated high-performance liquid chromatography (HPLC) method with fluorescence detection, which allowed 1 ng mL to be assayed as the lowest quantifiable concentration. From plasma concentrations, AUC0→t (the area under the plasma concentration-time curve from time 0 to the last sampling time, 32 hr), AUC0→∞ (the area under the plasma concentration-time curve from time 0 to infinity), t½ (elimination of half-life of the terminal log linear phase), Cmax (maximum plasma drug concentration) and Tmax (time to reach Cmax) were evaluated through noncompartmental pharmacokinetic analysis. AUC0→t and AUC0→∞ were calculated by the linear-log trapezoidal rule method. Cmax and Tmax were obtained directly from the plasma concentration-time curve. Analysis of variance was carried out using logarithmically transformed AUC0→t, AUC0→∞ and Cmax. As far as AUC0→t, AUC0→∞ and Cmax were concerned, there was no statistically significant difference between the test and reference formulations. Ninety percent confidence intervals (90% CI) for the ratio of AUC0→t, AUC0→∞ and Cmax values for the test and reference formulations were 100.4-107.8%, 99.0-107.2% and 87.5-111.3%, respectively. As the 90% CIs of AUC0→t, AUC0→∞ and Cmax were entirely within 80-125%, two formulations were considered bioequivalent.