生物等效性和生物利用度杂志

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Bioequivalence Evaluation of Two Formulations of Lamotrigine Tablets in Healthy Volunteers

Adriana Ruiz, Fanny Cuesta, Sergio Parra, Blanca Montoya, Margarita Restrepo, Lina Peña, Gloria Holguín and Rosendo Archbold

Lamotrigine is a phenyltriazine used in the treatment of epilepsy and bipolar disorder type I. The purpose of this study was to compare the bioavailability in healthy Colombian volunteers of two brands of lamotrigine 100 mg tablets: a new generic formulation (test product) developed by Humax Pharmaceuticals S.A (Medellín, Col) and LAMICTAL® (reference product) from Glaxo Operations UK Ltd (Ware, UK). A single-dose, randomized, two-period, two-sequence crossover study, with six weeks washout period, was performed. Blood samples were obtained from 0 to 144 hours after dosing and plasma lamotrigine levels were determined by a validated high performance liquid chromatographic (HPLC) method. The 90% confidence intervals (CIs) for the ratios of the ln AUC0-∞ and ln Cmax means between the reference and test formulations were constructed under 80/125 rule for bioequivalence limit. Fourteen subjects were enrolled in the study, but only twelve completed both treatment periods. The estimated pharmacokinetic parameters of lamotrigine for the reference and test formulations were Cmax 2.314 ± 0.414 µg/mL, 2.226 ± 0.355 µg/mL; AUC0-120 70.148 ± 10.824 µg.h/mL, 69.277 ± 13.432 µg.h/mL, and for AUC0-∞ were 78.524 ± 16.000 µg.h/mL, 77.532 ± 15.255 µg.h/mL, respectively. The 90% CIs for the ln-transformed ratio (test/reference) of AUC0-∞ and Cmax were 88.97 to 110.65 and 87.77 to 106.37, respectively.

Conclusions: In this single dose study it was found that the test and reference products of lamotrigine 100 mg tablets complied with the regulatory criteria for equivalence with respect to rate and extent of absorption according to the guidances of Instituto Nacional de Vigilancia de Medicamentos y Alimentos (INVIMA) and FDA.