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

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.