Review: Therapeutic Drug Monitoring in Pediatrics

Abstract

Therapeutic drug monitoring (TDM) can be defined as the measurement of drug concentrations in biologic fluids to assess whether they correlate with the patient's clinical condition and whether the dosage or dosage intervals need to be changed. This is done to optimize the management of patients receiving drug therapy for the alleviation or prevention of disease. Therapeutic drug monitoring is a relatively new service in the clinical pharmacology and toxicology laboratory and has evolved from being a luxury to a necessity. The principles of TDM were developed in the 1960s. Advances in research and knowledge and increasingly sophisticated laboratory methods led to an expansion of TDM (1-3).A drug must meet the following criteria to be eligible for monitoring:1. There should be a clinically interpretable correlation between the serum drug concentration and its pharmacologic effect. This usually implies a clinically significant correlation between the serum drug concentration and its concentration in the target tissue (1). There should be a better correlation between the plasma drug concentration and the pharmacologic effect than between the drug dosage and the pharmacologic effect. 2.A narrow margin should exist between serum concentrations that cause toxic effects and concentrations that produce therapeutic effects. 3.The serum concentration resulting from a given drug dose is unpredictable as a result of inter-and intraindividual differences in drug absorption, distribution, and elimination. Such poor correlation between serum concentration and drug dosage has been shown with clomipramine used in treatment of enuresis (2). 4.The pharmacologic effects of drugs are not readily measurable (e.g., suppression of seizure activity is difficult to monitor clinically when administering anticonvulsant drugs). 5.There must be a rapid and reliable method for the analysis of the drug.The criteria for monitoring drugs in children are the same as those for adults (6), but several additional factors must be considered. Neonates, infants, and children undergo major and rapid age-related physiologic and biochemical changes, especially during the first year of life, resulting in different clinical pharmacokinetic and pharmacodynamic parameters from adults (Table 1). Recent indications are that approximately 12% of all drugs prescribed in the United States are for children age 9 years and younger (4). Further, review of drug-

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“…Tais mudanças devem ser consideradas no momento da elaboração de esquemas terapêuticos, para que sejam atingidos os efeitos desejados com menor toxicidade. (Pezzani, 1993;Shirkey, 1999;Soldin, Soldin, 2002).…”

Improved solid‐phase microextraction device for use in on‐line immunoaffinity capillary electrophoresis

“…The qualitative and quantitative determination of drugs in body fluids, hair, nails, cells, and tissues is essential for therapeutic drug monitoring, forensic and clinical toxicology, drug metabolism, pharmacokinetic and drug development studies [1][2][3][4]. For many years, the development of analytical methodologies suitable for the accurate and reproducible determination of drugs, metabolic intermediates, xenobiotics, and endogenous biomolecules in complex matrices has been a challenge for pharmaceutical, forensic, and clinical chemists [5][6][7][8][9][10][11].…”

Practical pharmacokinetics: what do you really need to know?

“…By contrast, when dosed at less than the half-life, lower drug accumulation occurs with greater fluctuation in the peak and trough. The effective concentration and the safety profile of the drug needs to be considered to assess if large fluctuations are acceptable, for example, a higher once-daily gentamicin dose is acceptable despite its short half-life of approximately 3 h 4. It produces higher peak levels than the standard regime and this in turn increases the rate and extent of bacterial cell death, as well as lengthening the postantibiotic effect (suppression of bacterial regrowth) without increasing the risk of any drug toxicity 5…”

“…In neonates, the t 1/2 of phenobarbital is 67–99 h,4 so without a loading dose it could take 8–20 days to reach steady-state. Although drug half-lives are quoted in the literature, these represent average values mainly in adults, and should be used cautiously.…”