Low-dose lamotrigine co-administration decreases quetiapine plasma concentrations: Effect of UGT2B7-161C>T polymorphism in Japanese patients with depression.

Abstract

Objectives: Previous findings showing that lamotrigine co-administration decreases serum quetiapine concentrations were based solely on group comparisons using therapeutic drug monitoring databases. The present prospective study examined the effects of lamotrigine co-administration on plasma quetiapine concentrations in Japanese patients with depression and in relation to polymorphisms of UGT1A2 and UGT2B7, enzymes responsible for lamotrigine metabolism.

Materials and methods: 14 patients with depression were recruited in the study. They had been treated with immediate-release quetiapine 200, 400, or 700 mg/d. Lamotrigine was co-administered in all patients over a period of 8 weeks where the final doses of lamotrigine were 75 mg/d in 2 subjects taking valproate and 100 mg/d in 12 subjects not taking valproate. Blood samples were collected before and 2, 4, and 8 weeks after commencing lamotrigine co-administration. Quetiapine and lamotrigine concentrations in plasma were measured using LC/MS/MS. The genotypes of the UGT1A4 142T>G, UGT2B7-161C>T, and UGT2B7 372A>G polymorphisms were identified using real-time PCR analysis.

Results: The mean plasma concentration of quetiapine 8 weeks after lamotrigine treatment was significantly lower than that prior to the administration (p < 0.05). The mean percentage reduction in quetiapine concentration was significantly greater in subjects carrying the C/T and T/T genotypes when compared to those carrying the C/C genotype in respect to the UGT2B7-161C>T polymorphism (p < 0.05).

Conclusion: The present study provides evidence that low-dose lamotrigine co-administration decreases plasma quetiapine concentrations in Japanese patients with depression and that the magnitude of this effect differs between genotypes of the UGT2B7-161C>T polymorphism.