Elevation of Carbamazepine‐10, 11‐Epoxide by Quetiapine

Fitzgerald, Brian; Okos, A

doi:10.1592/phco.22.16.1500.33697

Cited by 38 publications

(17 citation statements)

References 9 publications

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“…17 Quetiapine also interacts with carbamazepine and increases the concentration of epoxide metabolite, possibly by inhibiting the epoxide hydroxylase enzyme. 18 It is also documented that valproic acid increases the incidence of carbamazepine-related toxic effects as well, due to accumulation of the epoxide metabolite in the plasma, despite total plasma carbamazepine concentrations within the therapeutic range. 14 The need for determination of carbamazepine and epoxide concentrations is clinically significant for select patient populations and clinical scenarios, wherein accumulation of the active epoxide level is likely.…”

Section: Discussionmentioning

confidence: 99%

Estimation of Carbamazepine and Carbamazepine-10,11-Epoxide Concentrations in Plasma Using Mathematical Equations Generated With Two Carbamazepine Immunoassays

et al. 2010

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Carbamazepine is metabolized to an active metabolite known as carbamazepine-10,11-epoxide, or simply the "epoxide" metabolite. The presence of this metabolite can have clinically significant implications in therapeutic drug monitoring of carbamazepine, but accurate quantification of the epoxide metabolite is currently limited to chromatographic techniques. In this study, mathematical equations are proposed for the estimation of carbamazepine and epoxide metabolite concentrations based on values generated by common carbamazepine immunoassays. Three immunoassays were studied: particle-enhanced turbidimetric inhibition immunoassay (PETINIA, Siemens Healthcare Diagnostics, Deerfield, IL), ADVIA Centaur (Siemens Healthcare Diagnostics), and a cloned enzyme donor immunoassay (CEDIA; Roche, Indianapolis, IN). Equations were based on observed cross-reactivity of epoxide with the PETINIA (average, 96.2%; range, 86.6%-105.7%) and epoxide cross-reactivity with the ADVIA Centaur assay (average, 6.5%; range, 5.3%-7.7%). In addition, equations were developed using average cross-reactivity of epoxide with the PETINIA and with the CEDIA. Values determined by calculation correlated well with carbamazepine and epoxide concentrations in supplemented and patient samples, for which values of carbamazepine (2.2-12.0 microg/mL [9-51 micromol/L]) and the epoxide metabolite (0.6-2.4 microg/mL) were also verified by liquid chromatography-tandem mass spectrometry.

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Section: Discussionmentioning

confidence: 99%

Estimation of Carbamazepine and Carbamazepine-10,11-Epoxide Concentrations in Plasma Using Mathematical Equations Generated With Two Carbamazepine Immunoassays

et al. 2010

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“…CYP3A4 inhibitors, like fluvoxamine and clozapine [46], and the antiepileptic agent phenytoin [47] may increase serum concentration of QTP, while inducers, like carbamazepine, enhance QTP metabolism [45], but it is also true that QTP itself can play the part of an isoenzyme inhibitor, inasmuch it may increase plasma levels of 10,11-dihydro-10,11-epoxycarbamazepine (the main active metabolite of carbamazepine) [48]. The inhibition of CYP3A4 due to fluconazole, ketoconazole and erythromycin should also be considered when using QTP [44].…”

Section: Pharmacokinetics and Interactionsmentioning

confidence: 99%

Antipsychotic and Antiepileptic Drugs in Bipolar Disorder: The Importance of Therapeutic Drug Monitoring

Musenga

Saracino

Sani³

et al. 2009

CMC

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Bipolar disorder (BD) is a long-term illness with mood swings which are characterized by recurrent episodes of mania/hypomania and depression, with variable interpolations of relatively asymptomatic periods, called euthymic, in which, however, some psychopathological symptoms may persist. Although mood stabilizers, such as lithium, are the first-line treatment for the prevention of new BD episodes, combination therapy has become the standard of care for BD patients. Besides lithium, the use of a mood stabilizer along with an atypical antipsychotic is recommended in many patients. Recently, atypical antipsychotics (quetiapine, olanzapine, risperidone and aripiprazole) and antiepileptic agents (valproate, lamotrigine and oxcarbazepine) are increasingly used as mood stabilizers. To reduce side effects and optimize treatment it is important to perform accurate monitoring of drug blood levels in these patients, who are often treated with multiple drugs. Therapeutic drug monitoring (TDM) is in fact a powerful tool that, starting from clinical-chemical correlation data, allows to tailor-cut treatment to the specific needs of individual patients; hence the need to have reliable analytical methods available for the determination of plasma levels of drugs and their metabolites. Analyses of biological samples are mainly carried out using high-performance liquid chromatography (HPLC) coupled with different detectors, capillary electrophoresis and gas-chromatography. Various procedures are employed to remove biological interferences before analyzing the samples. This review focuses on currently available analytical TDM methods for atypical antipsychotics and antiepileptic agents used in the treatment of patients with bipolar disorder. Advantages and limitations of the various analytical methods will be reviewed and discussed, together with an evaluation of the role of TDM.

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“…For example, lamotrigine may contribute to toxicity of carbamazepine through increasing the epoxide concentration by as much as 45% (12). Co-administration of quetiapine also increases the concentration of epoxide metabolite possibly by inhibiting the epoxide hydroxylase enzyme (13). Finally, valproic acid increases the incidence of carbamazepine-related toxicity due to accumulation of epoxide metabolite in the plasma, even when total plasma carbamazepine concentrations fall within the therapeutic range (7).…”

Section: Discussionmentioning

confidence: 99%

Discordant carbamazepine values between two immunoassays: carbamazepine values determined by ADVIA centaur correlate better with those determined by LC-MS/MS than PETINIA assay

McMillin

Juenke

Johnson

et al. 2011

J. Clin. Lab. Anal.

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Discordant carbamazepine values as determined by two different immunoassays may be due to different cross-reactivities with the active metabolite carbamazepine 10, 11-epoxide and may cause confusion in interpreting carbamazepine serum levels. In this study, we compared carbamazepine values in samples containing carbamazepine and the epoxide metabolite, as determined by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) and by two commercial carbamazepine immunoassays: the PETINIA and the ADVIA Centaur carbamazepine. Clinical specimens were used for the comparative studies wherein we determined carbamazepine concentrations using the PETINIA, ADVIA Centaur, and LC-MS/MS assays. We observed an excellent correlation between carbamazepine concentrations determined by the ADVIA Centaur and LC-MS/MS methods while carbamazepine values were overestimated using the PETINIA assay. When aliquots of drug-free serum were supplemented with clinically relevant concentrations of the carbamazepine epoxide metabolite, we observed negligible cross-reactivity of epoxide with the ADVIA Centaur assay but over 90% cross-reactivity with the PETINIA assay. We conclude that the ADVIA centaur assay accurately measures carbamazepine concentrations in plasma or serum and that the PETINIA assay significantly overestimates true carbamazepine concentration. Such discordance may cause confusion in interpreting serum carbamazepine levels.

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Elevation of Carbamazepine‐10, 11‐Epoxide by Quetiapine

Cited by 38 publications

References 9 publications

Estimation of Carbamazepine and Carbamazepine-10,11-Epoxide Concentrations in Plasma Using Mathematical Equations Generated With Two Carbamazepine Immunoassays

Estimation of Carbamazepine and Carbamazepine-10,11-Epoxide Concentrations in Plasma Using Mathematical Equations Generated With Two Carbamazepine Immunoassays

Antipsychotic and Antiepileptic Drugs in Bipolar Disorder: The Importance of Therapeutic Drug Monitoring

Discordant carbamazepine values between two immunoassays: carbamazepine values determined by ADVIA centaur correlate better with those determined by LC-MS/MS than PETINIA assay

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