DOI: http://dx.doi.org/10.18203/2319-2003.ijbcp20212072

Randomized, single-dose, two-period, two-sequence crossover bioequivalence study evaluating two oral formulations of lamotrigine in healthy volunteers

Murgan Panchatcharam, Sasidharan M., Sakthimanikandhan .

Abstract


Background: Lamotrigine is an anti-epileptic medicine used to treat epilepsy and bipolar disorder. The mechanism of action is to block voltage activated sodium channels. The aim of this study was to evaluate the bioequivalence of 2 oral formulations of lamotrigine 25 mg in healthy volunteers.

Methods: A single-dose, two-period, randomized crossover study design in - healthy Indian adult volunteers was conducted at Amaris Clinical, a division of Caplin Point Laboratories Ltd., Chennai. A validated high performance liquid chromatography in conjunction with mass spectrometry was used. Lamotrigine concentration in plasma. Adverse events were determined by measuring vital functions after dosing. A total of 24 subjects were included.

Results: The mean and 90% confidence intervals of the test / reference ratios for these parameters were as follows: The mean Cmax and Tmax of the test were 758.606 (157.453) ng / ml and 1.17 (0.50-5.00) hours, respectively. The mean Cmax and Tmax of the reference were 775.993 (151.654) ng / ml or 0.88 (0.25-4.00) hours. The mean AUC0-72 was 24142. 031±3641.691 (ng.hr/mL) for the test formulation and 24202.099±3742.957 (ng. h / ml) for the reference formulation. The mean test / reference ratios for Cmax and AUC0-72 were 97.92 and 99.82 respectively. The 90% parametric CIs for Cmax and AUC0-72 were 90.17-105.68% or 97.87-101.81%.

Conclusions: The 90% confidence intervals ranged from 80-125% and it was concluded that the test product was bioequivalent to the reference product in these healthy adult male volunteers. 


Keywords


Bioequivalent, Lamotrigine, Pharmacokinetics, Reference, Test

Full Text:

PDF

References


Bhagwagar Z, Goodwin GM. Lamotrigine in the treatment of bipolar disorder. Expert Opin Pharmacother. 2005;6(8):1401-8.

Machado-Vieira R, Ibrahim L, Henter ID, Zarate CA Jr. Novel glutamatergic agents for major depressive disorder and bipolar disorder. Pharmacol Biochem Behav. 2012;100(4):678-87.

Zarate C Jr, Machado-Vieira R, Henter I, Ibrahim L, Diazgranados N, Salvadore G. Glutamatergic modulators: the future of treating mood disorders? Harv Rev Psychiatry. 2010;18(5):293-303.

Pilc A, Wierońska JM, Skolnick P. Glutamate-based antidepressants: preclinical psychopharmacology. Biol Psychiatry. 2013;73(12):1125-32.

Goldsmith DR, Wagstaff AJ, Ibbotson T, Perry CM. Spotlight on lamotrigine in bipolar disorder. CNS Drugs. 2004;18(1):63-7.

Peck AW. Clinical pharmacology of lamotrigine. Epilepsia. 1991;32(2):S9-12.

ORGANIZACIÓN PANAMERICANA de la SALUD – ORGANIZACIÓN MUNDIAL de la SALUD OPS/OMS (2002) Normas éticas internacionales para las investigaciones biomédicas con sujetos humanos.

European Medicines Agency. International conference on harmonisation. Guideline for good clinical practice. ICH topic E6. 2005.

Rambeck B, Wolf P. Lamotrigine clinical pharmacokinetics. Clin Pharmacokinet. 1993;25:433-43.

Goa KL, Ross SR, Chrisp P. Lamotrigine: a review of its pharmacological properties and clinical efficacy in epilepsy. Drugs. 1993;46:152-76.

Food and Drug Administration. Guidance for industry, bioavailability and bioequivalence studies for orally administered drug products. 2003.

Srichaiya A, Longchoopol CH, Oo-Puthinan S, Sayasathid J, Sripalakit P. Bioequivalence of generic lamotrigine 100-mg tablets in healthy Thai male volunteers: a randomized, single-dose, two-period, two-sequence crossover study. Clin Ther. 2005;30:1844-51.

Ruiz A, Cuesta F, Parra S, Montoya B, Restrepo M, Archbold R, et al. (2012) Bioequivalence Evaluation of Two Formulations of Lamotrigine Tablets in Healthy Volunteers. J Bioequiv Availab. 2012;4:030-4.