Plasma clozapine and norclozapine in relation to prescribed dose and other factors in patients aged <18 years: data from a therapeutic drug monitoring service, 1994–2010

Abstract

As in adults, clozapine TDM may help in assessing adherence and in dose adjustment, for example if smoking habit changes.

Reliable clinical serum analysis with reusable electrochemical sensor: Toward point-of-care measurement of the antipsychotic medication clozapine

“…In fact, clozapine’s side effect risks led to its removal from the market, but it was later re-introduced because of its unique therapeutic benefits (Warnez and Alessi-Severini, 2014; Wenthur and Lindsley, 2013). As illustrated in Figure 1a, the challenge to clinicians is that serum clozapine levels cannot be adequately controlled by dosage because of variabilities in drug metabolism (Couchman et al, 2013; Rajkumar et al, 2013; Rostami-Hodjegan et al, 2004). A recent survey indicated that clozapine would be more broadly prescribed if serum levels could be rapidly measured at the point-of-care (POC) to provide clinicians with the timely information required to adjust dosages (Kelly et al, 2015).…”

Drug interactions affecting clozapine levels

“…In our review, drug interactions resulted in wide variability in the increased plasma norclozapine levels from 101 to 1559 ng ml 21 . The practical use of the clozapine:norclozapine ratio was reported by Couchman et al (2013). The practical use of the clozapine:norclozapine ratio was reported by Couchman et al (2013).…”

“…Clozapine is 97% bound to plasma proteins and has a mean half-life of about 12 hours (range 6-33 hours). The therapeutic drug monitoring (TDM) of clozapine, and of its principal plasma metabolite N-desmethyl clozapine (norclozapine), has been shown to assist management by: identifying or confirming suspected non-adherence; assessing whether clozapine is being used at a therapeutic dose; and minimising the risk of dose-related toxicity (Couchman et al 2013). There are variety of analytical methods to assay clozapine and its metabolite including high performance liquid chromatography, gas chromatography, gas chromatography/ mass spectrometry and radio-immunoassay (Cooper, 1996).…”

“…Medications interfering with the activity of these cytochrome enzymes results in changes in plasma clozapine levels. Results for both clozapine and norclozapine below the tenth percentile are taken to suggest recent poor adherence, although rapid metabolism (notably in young, male, smokers) cannot always be excluded (Couchman et al 2013). Plasma clozapine concentrations in the range of 0.35-0.60 mg l 21 are associated with a good antipsychotic response in many adult patients, although the upper limit remains a subject of debate (Hiemke et al 2004;Khan & Preskorn 2005;Taylor et al 2009).…”

“…The therapeutic drug monitoring (TDM) of clozapine, and of its principal plasma metabolite N-desmethyl clozapine (norclozapine), has been shown to assist management by: identifying or confirming suspected non-adherence; assessing whether clozapine is being used at a therapeutic dose; and minimising the risk of dose-related toxicity (Couchman et al 2013). Norclozapine has a longer plasma half-life than clozapine in patients who have been taking the drug chronically, hence plasma norclozapine shows less day-to-day variation than plasma clozapine (Couchman et al 2013). The threshold for therapeutic response may be lower once a degree of symptom control has been achieved (Yusufi et al 2007).…”