Effect of adjunctive lamotrigine treatment on the plasma concentrations of clozapine, risperidone and olanzapine in patients with schizophrenia or bipolar disorder

被引:27
作者
Spina, Edoardo
D'Arrigo, Concetta
Migliardi, Gaetana
Santoro, Vincenza
Muscatello, Maria Rosaria
Mico, Umberto
D'Amico, Giuseppina
Perucca, Emilio
机构
[1] Univ Messina, Dept Clin & Expt Med & Pharmacol, Pharmacol Sect, Policlin Univ Messina, I-98125 Messina, Italy
[2] IRCCS, Ctr Neurolesi Bonino Pulejo, Messina, Italy
[3] Univ Messina, Dept Neurosci Psychiat & Anesthesiol Sci, I-98100 Messina, Italy
[4] Univ Pavia, Dept Internal Med & Therapeut, Clin Pharmacol Unit, I-27100 Pavia, Italy
[5] IRCCS C Mondino Fdn, Inst Neurol, Pavia, Italy
关键词
lamotrigine; clozapine; olanzapine; risperidone; drug interaction; pharmacokinetics;
D O I
10.1097/01.ftd.0000246763.59506.b0
中图分类号
R446 [实验室诊断]; R-33 [实验医学、医学实验];
学科分类号
1001 ;
摘要
The effect of lamotrigine on the steady-state plasma concentrations of the atypical antipsychotics clozapine, olanzapine, and risperidone was investigated in patients with schizophrenia or bipolar disorder stabilized on chronic treatment with clozapine (200500 mg/day; n = 11), risperidone (3-6 mg/day; n = 10) or olanzapine (10-20 mg/day; n = 14)). Lamotrigine was titrated up to a final dosage of 200 mg/day over 8 weeks, and pharmacokinetic assessments were made at baseline and during treatment weeks 6 and 10, at lamotrigine dosages of 100 and 200 mg/day respectively. The plasma concentrations of clozapine, norclozapine, risperidone, and 9-hydroxyrisperidone did not change significantly during treatment with lamotrigine. The mean plasma concentrations of olanzapine were 31 +/- 7 ng/mL at baseline, 32 +/- 7 ng/mL at week 6, and 36 +/- 9 ng/mL at week 10, the difference between week 10 and baseline being statistically significant (P < 0.05). Adjunctive lamotrigine therapy was well tolerated in all groups. These findings indicate that lamotrigine, at the dosages recommended for use as a mood stabilizer, does not affect the plasma levels of clozapine, risperidone, and their active metabolites. The modest elevation in plasma olanzapine concentration, possibly due to inhibition of UGT1A4-mediated olanzapine glucuronidation, is unlikely to be of clinical significance.
引用
收藏
页码:599 / 602
页数:4
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