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Author: Admin | 2025-04-28
Days for chlorpromazine. It has little relevance to the desired effect of the drug, even though it represents mechanisms which keep significant amounts in the body for long periods with what is, after all, a very long-acting drug. However, it probably has considerable significance, in ways poorly understood at present, for toxicity.Of considerable interest is the recent observation that the half-life of neuroleptic activity as measured by means of the radioreceptor assay is as much as 15–17 days after administration of haloperidol to rats (Cohen et al., 1988). Generally speaking, rats eliminate drugs more rapidly than do humans, so from this data we might predict a very long half-life in humans. Also, a neuroleptic assay will include active metabolites with most drugs (although to a relatively minor extent with haloperidol). It should be noted that Irene Forrest and co-workers, over 30 years ago, reported that drug-derived material was detectable in urine for as long as 2 years following cessation of chlorpromazine treatment. Thus, without doubt, neuroleptic drugs persist in one form or another for a very long time, and this probably has significance for the relapse times after stopping dosing. However, since the route from the brain is via plasma, it is probably erroneous to think that neuroleptic drugs and their metabolites are ever present in tissues but absent from plasma. What actually happens is that they become analytically undetectable in plasma while still present in tissues (and detectable in urine). This was recently shown clearly with promazine (Curry & Hu, 1990).Read full chapterURL: https://www.sciencedirect.com/science/article/pii/B97801207903575001544.04.2.1.3 Half-lifeThe elimination half-life (t½) is the time it takes for the drug concentration to decrease by one-half. The half-life is a function of the Vd and the total CL of a drug as shown in Eq. (2).(2)t½=Vd×loge2/CLThis relationship is such that the larger the total clearance, the shorter the half-life and, conversely, the larger the Vd, the longer the half-life.19,20Half-life is used to determine the optimal frequency of drug administration for chronically administered medicines. Often, drugs are administered every half-life in order to minimize the difference between peak and trough drug concentrations over the dosing
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