Bioequivalence assessment of two pregabalin capsules in healthy Mediterranean Arab volunteers.

BACKGROUND

Treatment of neuropathic pain has always been challenging, not only from the pharmaco-therapeutic/toxicological point of view, but also due to the unpredictable pharmacokinetic (PK) variations among different generic formulations of the same drug, which require further dose optimization.

OBJECTIVES

This progressive work aims to evaluate the bioequivalence (BE) of a generic product of 150 mg pregabalin capsule (antineuropathic drug) vs. the reference brand drug Lyrica^®. <u>

METHOD: </u> An LC-MS/MS bioanalytical method was developed and validated according to the International Conference on Harmonization (ICH) guidelines in order to be used for the analysis of pregabalin in plasma. BE of capsules was tested by comparison against the reference brand capsules in accordance with the requirements of the declarations of Helsinki, the current Good Clinical Practice (GCP) Guidelines and the ICH. The resulting data were compared against corresponding pregabalin data published on other human races.

RESULTS

The relationship between concentration and peak area ratio was found to be linear within the range 0.096 - 6.068 µg/mL for pregabalin. The correlation coefficient (r) was equal to 0.9983. Statistical comparison of the main PK parameters showed no significant difference between test and reference. The mean Cmax values for test and reference were 4.290 and 4.164 µg/mL, and the mean AUC0-last values were 24.275 h×µg/mL and 23.674 h×µg/mL, respectively. The 90% CIs of geometric mean ratios (test/reference) for pregabalin were 100.34 - 104.78%, 100.34 - 104.70%, and 95.65 - 110.96% for AUC0-last, AUC0-∞, and Cmax, respectively, thus fall within the international specified BE limit (80 - 125%). Both products were well tolerated by all the volunteers and there were no significant differences on physical examination or in vital signs and laboratory tests between groups. All volunteers completed the study and were discharged in good health.

CONCLUSION

The tested generic capsules appear to be bioequivalent to the reference brand and are expected to have a similar efficacy and safety profile.