Background Plasma levels of imipramine vary widely between individuals. They are probably due to genetic polymorphism and inter-individual differences in the metabolism of imipramine.
Purpose The objective of this study was to obtain pharmacokinetic data and compare the relative bioavailability of generic imipramine 25 and 50 mg tablets (Sobhan Pharmaceuticals, Iran) with the reference product (Tofranil, Ciba Geigy Pharmaceuticals, England).
Materials and methods Fourteen healthy male volunteers received a single oral dose (100 mg) of the generic and reference formulations following overnight fasting in a double blind, randomised, crossover study. Blood samples were collected and the plasma concentrations of imipramine were determined by using a rapid and selective reverse phase high-performance liquid chromatographic (HPLC) method. Plasma data was used to evaluate relative bioavailability and other pharmacokinetic parameters such as AUC, Cmax, Tmax, etc.
Results The mean peak plasma concentration (Cmax) of imipramine for different tablet formulations, A (reference) and B (test), were 95.83±14.00 ng/ml (A50), 144.33±30.17 ng/ml (A25), 112.70±9.31 ng/ml (B50) and 141.00±26.86 ng/ml (B25) at 3.25±0.24 h (A50), 2.83±0.24 h (A25), 3.25±0.25 h (B50) and 2.90±0.28 h (B25) respectively. The mean AUC0-∞ of the different formulations, A and B, were 511.22±58.99 ng h ml-1 (A50), 770.49±132.40 (A25), 512.9±75.82 (B50) and 821.06±159.00 (B25).
Conclusions Statistical analysis showed no significant differences between the various pharmacokinetic parameters of the different formulations. The 90% CI for the mean ratios (the test against the reference formulation) of the Cmax, AUC0-24 and AUC0-∞ were within the FDA requirements (80-125%). There was a significant difference between the dissolution rates of the different dosage forms (p<0.001). Results of this study showed that despite of a lower dissolution rate, the generic formulation of imipramine tablets are bioequivalent to the reference product with respect to the rate and extent of absorption.
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