Therapeutic drug monitoring indications

TABLE 4.2 Indications for Therapeutic Drug Monitoring of Psychotropic Drugs... 

Another use of the laboratory is for therapeutic drug monitoring (TDM) of psychotropics with defined optimal ranges, narrow therapeutic indices, or both. Although TDM is not essential for many psychotropics, it is for others, including lithium, several TCAs, valproate, and carbamazepine. It may also be helpful to optimize the use of certain antipsychotics (e.g., haloperidol, clozapine) ( 7). 

Therapeutic drug monitoring, 101-110 analytical techniques, 105 by immunoassay, 158 choice of drug, 103 choice of sample, 103 indications for, 102 interpretation of results, 106 timing of measurements, 104 Thermal conductivity detector, 183 Thiabendazole, 85,1012 Thiacetazone, 1013 Thiacyl, 978 Thialbarbital, 1014 Thialbarbitone, 1014 Thialbarbitone sodium, 1014 Thiamazole, 750 Thiambutosine, 1014 Thiamine, 1014 in sport, 99... 

A review of the literature on clozapine and therapeutic drug monitoring (11 reviews, 24 studies, 35 case reports) found evidence indicating a dose-relafed (500-600mg per day) increased risk of seizures [99 ]. There were limited data suggestive of a relationship between plasma levels, dose, and side effects such as seizures, myocarditis and agranulocytosis. 

Monitoring plasma and blood levels of the drug, if indicated, to ensure therapeutic levels and compliance with medication. Supporting the patient s compliance with treatment anticipat-... 

Cross-reactivity (an indicator of assay specificity) has critical importance for immunoassay methods in which a particular analyte is assayed in the presence of very similar species for example, in the monitoring of a therapeutic drug in serum where various metabolites of the drug are also present. For the sake of uniformity, cross-reactivity is usually reported as the mass or concentration of interferent... 

Because fluoroquinolones have a wide therapeutic index and dose-dependent toxicity, routine drug monitoring is not indicated. Monitoring fluoroquinolone concentration is indicated in renal failure, which wfll cause fluoroquinolones to accumulate. Optimal response occurs when serum concentration exceeds 1.5 Llg/mL. Activity is maintained as long as the trough concentration is >0.2flg/mL. Coadministration with antacids, ferrous sulfate, food, or sucralfate reduces absorption by 30% to 60%. Co-administration with morphine reduces absorption by >50%. 

Phase II investigates the compound s efficacy and safety in controlled clinical trials for a specific therapeutic indication. To eliminate as many competing factors as possible, Phase II trials are narrowly controlled. They are characterized as small—several hundred subjects with the indicated disease or symptoms—and are closely monitored. The control may be either a placebo study arm or an active control arm. The endpoint measured may be the clinical outcome of interest or a surrogate. Phase II trials may last for several months or even several years. Early pilot trials to evaluate safety and efficacy are called Phase Ila. Later trials, called Phase lib, are important tests of the compound s efficacy. These trials may constitute the pivotal trials used to establish the drug s safety and efficacy. At least one pivotal trial (most frequently a large, randomized Phase III study) is done. Only about one third of compounds entered into Phase II will begin Phase III studies [61],... 

Initial therapeutic exploratory studies may use a variety of study designs, including concurrent controls and comparison with baseline status. Subsequent trials are usually randomized and concurrently controlled to evaluate the efficacy of the drug and its safety for a particular therapeutic indication. Studies in Phase II are typically conducted in a group of patients who are selected by relatively narrow criteria, leading to a relatively homogeneous population, and are closely monitored. 

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