Bioequivalence of generic lamotrigine 100-mg tablets in healthy Thai male volunteers: a randomized, single-dose, two-period, two-sequence crossover study.

BACKGROUND

Lamotrigine is an antiepileptic drug which has been used in the treatment of epilepsy and bipolar disorder. A search of the literature did not find previously published bioequivalence and pharmacokinetic evaluations of lamotrigine in healthy Thai male volunteers.

OBJECTIVE

The aim of this study was to compare the pharmacokinetic parameters between 2 brands of lamotrigine in healthy Thai male volunteers.

METHODS

A randomized, single-dose, 2-period, 2-sequence, crossover study design with a 2-week washout period was conducted in healthy Thai males. Subjects were randomized to receive either the test or reference formulation in the first period. All subjects were required to be nonsmokers and without a history of alcohol or drug abuse. Plasma samples were collected over a 120-hour period after 100-mg lamotrigine administration in each period. A validated high-performance liquid chromatography ultraviolet method was used to analyze lamotrigine concentration in plasma. Pharmacokinetic parameters were determined using a noncompartmental method. Bioequivalence between the test and reference products, as defined by the US Food and Drug Administration (FDA), is determined when the ratio for the 90% CIs of the difference in the means of the log-transformed AUC(0-t), AUC(0-infinity), and C(max) of the 2 products are within 0.80 and 1.25. Adverse events were determined by measuring vital signs after dosing. Subjects were also asked if they suffered from undesirable effects such as nausea, vomiting, dizziness, and headache.

RESULTS

This bioequivalence study was performed in 24 healthy Thai males (mean [SD] age, 20.5 [1.3] years; range, 19-24 years; weight, 62.5 [7.4] kg; height, 172.8 [6.9] cm; body mass index, 20.9 [2.0] kg/m(2)). The mean (SD) C(max) and T(max) of the test formulation of lamotrigine were 1.7 (0.3) microg/mL and 1.2 (0.9) hours, respectively. The mean (SD) C(max) and T(max) of the reference formulation of lamotrigine were 1.7 (0.3) microg/mL and 1.4 (1.0) hours, respectively. The mean (SD) AUC(0-t) was 67.1 (13.2) microg/mL x h(-1) for the test product and 66.4 (14.6) microg/mL x h(-1) for the reference product. The mean (SD) AUC(0-infinity) was 74.9 (18.3) microg/mL x h(-1) for the test product and 74.3 (20.5) microg/mL x h(-1) for the reference product. The mean (SD) t((1/2)) values were 35.0 (7.6) hours for the test product and 34.7 (7.6) hours for the reference product. The mean test/reference ratios for AUC(0-t), AUC(0-infinity), and Cmax were 1.01, 1.01, and 1.05, respectively. The parametric 90% CIs for AUC(0-t), AUC(0-infinity), and Cmax were 0.98 to 1.05, 0.98 to 1.06, and 0.98 to 1.13, respectively. Following administration, dizziness or headache was reported in 2 subjects in the test group and 1 subject in the reference group.

CONCLUSION

The results of this study suggest that the test product was bioequivalent to the reference product in these healthy Thai male subjects, based on the US FDA's regulatory definition.