Pharmacokinetic Comparison Of A Generic Flupentixol-Melitracen Tablets And The Innovator Preparation In Humans

OBJECTIVESTo investigate pharmacokinetics of a generic flupentixol-melitracen tablets and the innovator preparation in humans, and evaluate the difference of pharmacokinetic parameters and the relative bioavailability and bioequivalence of Flupentixol-Melitracen tablets in the human body.METHODSIn a randomized, open-label, two-period crossover, single-dose trail,18 healthy male subjects were randomized into two groups. A single oral dose of Flupentixol-Melitracen tablets was given to the two groups. Group One first received the generic preparation, and then followed by the innovator preparation; while Group Two received the innovator preparation first, and followed by the generic preparation. Blood samples were taken at scheduled time spots. Plasma concentration of Flupentixol-Melitracen was measured by HPLC-MS. Pharmacokinetic parameters were calculated by DAS 2.0. ANOVA was used to check the difference of the means of the pharmacokinetic parameters between the two preparations. Bioequivalence was determined by two one-sided t-tests.RESULTS18 healthy volunteers received a single oral dose of three tablets generic flupentixol-melitracen tablets or the innovator preparation. One-compartmental model was adopted as the appropriate pharmacokinetics model to analysis pharmacokinetics of flupentixol and melitracen.The non-compartmental pharmacokinetic parameters of Flupentixol, AUC0→96h, AUC0→∞, tmax and Cmax of the 18 subjects after taking a single dose of the trial preparation or the reference preparation (3 tablets) were 17.73±6.86μg·h·L-1 and 18.98±7.12μg·h·L-1,20.33±7.62μg·h·L-1 and 21.59±7.91μg·h·L-1,5.5±2.0 h and 5.6±1.8 h,0.631±0.262μg·L-1 and 0.635±0.274μg·L-1, respectively. The relative bioavailability of Flupentixol was 94.77±16.10%. The non-compartmental pharmacokinetic parameters of Melitracen, AUC0→96h, AUC0→∞, tmax and Cmax of the 18 subjects after taking a single dose of the trial preparation or the reference preparation (3 tablets) were 557.2±234.2μg·h·L-1 and 554.8±264.1μg·h·L-1,602.9±262.0μg·h·L-1 and 601.2±279.9μg·h·L-1,5.4±1.5 h and 5.2±1.1 h,20.19±6.69μg·L-1 and 18.85±7.01μg·L-1, respectively. The relative bioavailability of Melitracen was 100.42±14.82%. No significant differences were found between the main pharmacokinetic parameters of the two components by ANOVA, and the two one-sided t-tests showed that the trial preparation and the reference preparation were bioequivalent.CONCLUSIONSThere was no difference of pharmacokinetic parameters between a generic flupentixol-melitracen Tablet and the innovator preparation in humans. The generic flupentixol-melitracen Tablet was bioequivalent to the innovator preparation.