Literature Values of Terminal Half-Lives of Clozapine are Dependent on the Time of the Last Data Point

The pharmacokinetics of clozapine is a subject of intensive research because of its narrow therapeutic window and susceptibility to drug-drug interactions. A systematic literature search was conducted in PubMed and Google Scholar for half-life values of clozapine in humans. Twenty-one publications were found to contain terminal half-life information of clozapine in humans along with the time of the last plasma sample. Average values of the terminal half-lives of clozapine were calculated to be 10.2, 13.2, 14.2, 18.3 and 29.2 hours with a last data point at 12, 24, 48, 72 and 120 hours, respectively. This confirms the notion that one would arrive at longer terminal half-lives when longer blood sampling times are used in pharmacokinetic studies on clozapine. “Terminal half-lives” of therapeutic agent are routinely computed and reported in literature. For drugs with a third deep compartment such as clozapine, one should remember to consider the time of the last data point when comparing the “terminal” half-life.