Clozapine, Serum or Plasma

Clozapine is absorbed rapidly, with peak plasma concentrations occurring within 30 minutes to six hours. Terminal half-life in humans is in the range of 5.5 to 33 hours. Determination of clozapine in plasma is needed to correlate efficacy with plasma concentration. However, pharmacogenomics and coadministration of other agents can complicate the correlation between dose and plasma concentration. Changes in the activity of the cytochrome P450 mixed-function oxidases, especially CYP1A2 and CYP3A4 can affect clozapine levels.¹ These oxidases can be induced by drugs such as carbamazepine, with the resulting increase in activity causing 50% decrease in clozapine concentration.² An additional report³ has indicated some patients may be ultrarapid metabolizers of clozapine due to genetically induced CYP1A2 activity levels. Conversely, clozapine plasma (serum) concentrations may be increased by inhibitors of the P450 oxidases. Amiodarone, cimetidine, ciprofloxacin, fluoxetine, fluvoxamine, indinavir, paroxetine, quinidine, ritonavir, and saquinavir are examples of inhibiting drugs which may cause increases in clozapine levels when coadministered.

A review of adverse metabolic effects⁴ has indicated clozapine can significantly increase mean levels of glucose and C-peptide, as well as increase in triglyceride levels. Additionally, the Federal Drug Administration and drug provider have issued the following: Patients being treated with clozapine must have a baseline white blood cell (WBC) count and absolute neutrophil count (ANC) before initiation of treatment as well as regular WBC counts and ANCs during treatment and for at least four weeks after discontinuation of treatment.⁵