BACKGROUND: Quetiapine is an atypical antipsychotic drug that was recently also approved for the treatment of uni- and bipolar depression. The antidepressive response is considered to be mediated by the metabolite N-desalkylquetiapine, and the aim of this study was to assess the interindividual pharmacokinetic variability of quetiapine and N-desalkylquetiapine in psychiatric patients based on therapeutic drug monitoring samples. METHODS: Serum measurements of quetiapine and N-desalkylquetiapine performed between October 2007 and July 2008 were retrospectively included from a routine therapeutic drug monitoring database. Pharmacokinetic variability was expressed as the 5-95 percentile range in dose-adjusted serum concentrations (C/D ratios). The impact of age (65 years or older), gender, and sampling time on the C/D ratios was studied by linear mixed model analysis. Samples from patients comedicated with CYP3A4 inducers or inhibitors were examined separately. RESULTS: In total, 927 serum samples from 601 patients were included (all using quetiapine immediate-release tablets). The 5-95 percentiles of the C/D ratio ranged 15-fold (0.14-2.1 nmol/L/mg) for quetiapine and fivefold (0.44-2.1 nmol/L/mg) for N-desalkylquetiapine. Elderly (65 years or older) obtained 1.5- and 1.2-fold higher C/D ratios of quetiapine (P = 0.002) and N-desalkylquetiapine (P = 0.03) compared with younger patients, respectively. Sampling time was also found to significantly affect the C/D ratios of quetiapine (P = 0.001), whereas gender was not a significant variable (P > 0.13). In three patients treated with potent CYP3A4 inducers, the observed C/D ratios of quetiapine and N-desalkylquetiapine were 77% and 11% lower than the mean C/D ratio in the study population, respectively. CONCLUSION: The pharmacokinetic variability was greater for quetiapine compared with N-desalkylquetiapine. Age 65 years or older and comedication with CYP3A4 inducers affected the serum levels of both agents, but the relative impact was greater on quetiapine.
BACKGROUND:Quetiapine is an atypical antipsychotic drug that was recently also approved for the treatment of uni- and bipolar depression. The antidepressive response is considered to be mediated by the metabolite N-desalkylquetiapine, and the aim of this study was to assess the interindividual pharmacokinetic variability of quetiapine and N-desalkylquetiapine in psychiatricpatients based on therapeutic drug monitoring samples. METHODS: Serum measurements of quetiapine and N-desalkylquetiapine performed between October 2007 and July 2008 were retrospectively included from a routine therapeutic drug monitoring database. Pharmacokinetic variability was expressed as the 5-95 percentile range in dose-adjusted serum concentrations (C/D ratios). The impact of age (65 years or older), gender, and sampling time on the C/D ratios was studied by linear mixed model analysis. Samples from patients comedicated with CYP3A4 inducers or inhibitors were examined separately. RESULTS: In total, 927 serum samples from 601 patients were included (all using quetiapine immediate-release tablets). The 5-95 percentiles of the C/D ratio ranged 15-fold (0.14-2.1 nmol/L/mg) for quetiapine and fivefold (0.44-2.1 nmol/L/mg) for N-desalkylquetiapine. Elderly (65 years or older) obtained 1.5- and 1.2-fold higher C/D ratios of quetiapine (P = 0.002) and N-desalkylquetiapine (P = 0.03) compared with younger patients, respectively. Sampling time was also found to significantly affect the C/D ratios of quetiapine (P = 0.001), whereas gender was not a significant variable (P > 0.13). In three patients treated with potent CYP3A4 inducers, the observed C/D ratios of quetiapine and N-desalkylquetiapine were 77% and 11% lower than the mean C/D ratio in the study population, respectively. CONCLUSION: The pharmacokinetic variability was greater for quetiapine compared with N-desalkylquetiapine. Age 65 years or older and comedication with CYP3A4 inducers affected the serum levels of both agents, but the relative impact was greater on quetiapine.
Authors: Nageshwar R Budha; Tao Ji; Luna Musib; Steve Eppler; Mark Dresser; Yuan Chen; Jin Y Jin Journal: Clin Pharmacokinet Date: 2016-11 Impact factor: 6.447
Authors: Martino Belvederi Murri; Argentina Guaglianone; Michele Bugliani; Pietro Calcagno; Matteo Respino; Gianluca Serafini; Marco Innamorati; Maurizio Pompili; Mario Amore Journal: Drugs R D Date: 2015-03