Pediatric patients dose determination

A correct dose of medication for a pediatric patient is determined by... 

In 2005, a study appeared in Cancer Letters that would have evoked widespread media coverage if it had been about an illegal drug, rather than about a pharmaceutical company product (El-Zein, 2005). Researchers from the University of Texas examined 12 children treated with therapeutic effects of Ritalin to determine whether this central nervous system stimulant produces cytogenetic abnormalities in pediatric patients at therapeutic doses. Using peripheral blood lymphocytes taken from the children, they found a 2.4-fold increase in chromosome aberrations and similar defects. They concluded, These findings warrant further investigations of the possible health effects of methylphenidate in humans, especially in view of the well-documented relationship between elevated frequencies of chromosome aberrations and increased cancer risk. ... 

Nerve agent exposures must be handled quickly and efficiently. When children are exposed, it is important to remember that antidote dosing will be determined by the patient s weight and the severity of exposure. Progress has been made to provide pediatric-specific autoinjectors however, since 2-PAM Cl is not yet available in a pediatric autoinjector form, it is possible to carefiilly use adult autoinjectors to manage pediatric patients. 

Drugs for pediatric patients should be dosed on a mg/ kg or a mg/m basis using information available for the patient s age group. In addition, the patient s renal and hepatic functions must be considered. The route for administration must be determined based on the severity of the illness, the availability of the medication for a particular route of administration, and whether the patient is able to take a medication orally. 

Dosing for pediatric patients in the 50-70 kg range can be more closely titrated by using a ratio to determine dose/kg 1/70 x adult dose = dose/1 kg. 

The AEGL-1 concentration was based on a 1-hour (h) no-effect concentration of 8,000 parts per million (ppm) in healthy human subjects (Emmen et al. 2000). This concentration was without effects on pulmonary function, respiratory parameters, the eyes (irritation), or the cardiovascular system. Because this concentration is considerably below that causing any adverse effect in animal studies, an intraspecies uncertainty factor (UF) of 1 was applied. The intraspecies UF of 1 is supported by the absence of adverse effects in therapy tests with patients with severe chronic obstructive pulmonary disease and adult and pediatric asthmatics who were tested with metered-dose inhalers containing HFC-134a as the propellant. Because blood concentrations in this study approached equilibrium following 55 minutes (min) of exposure and effects are determined by blood concentrations, the value of 8,000 ppm was made equivalent across all time periods. The AEGL-1 of 8,000 ppm is supported by the absence of adverse effects in experimental animals that inhaled considerably higher concentrations. No adverse effects were observed in rats exposed at 81,000 ppm for 4 h (Silber and Kennedy 1979) or in rats exposed... 

Medical illness or medication side effects may directly affect cognition virtually all classes of medication have been implicated. In adult patients, glucocorticoids can impair memory at relatively low doses (Keenan et ah, 1995 Newcomer et ah, 1999), as there are postulated effects on hippocampal neurons. Newcomer et ah, (1999) have reviewed the literature on illnesses in adults in which memory inversely correlates with cortisol levels, such as in Cushing s disease, Alzheimer s dementia, schizophrenia, and depression. There is no similar literature on the pediatric population. The risk of memory impairment puts chronic steroid treatment, such as that seen in certain pediatric rheumatologic disorders and severe asthmatics, for example, into a different perspective, however. Documentation of memory both before and during chronic steroid treatment might help determine detrimental effects in the pediatric population. 

Very few examples of outcomes research in neurological pharmacy exist. However, one historical control study determined that the implementation of a pharmacokinetics consultation service in an epilepsy clinic decreased seizure frequency and number of adverse effects compared with the baseline frequency in the 4 months prior to offering the service.A second study conducted in the pediatric epilepsy population described the effect of establishment of a specialty pediatric epilepsy clinic with clinical pharmacy services. Compared with patients seen before the beginning of the clinic, patients seen in the specialty clinic had decreased numbers of antiepileptic drugs and decreased doses of these medications. Frequency of seizures was not examined in this report. 

Interpatient variability in the pharmacokinetics of oral methotrexate and mercaptopurine may also be an important determinant of the effectiveness and toxicity of maintenance therapy. Patients who take their oral methotrexate and mercaptopurine on an evening versus a morning schedule appear to have a superior outcome. To account for the interpatient variability, most pediatric protocols titrate the dose of either agent to maintain an absolute neutrophil count of 750 to 1,500/rmn. Some protocols circumvent bioavailabihty and poor compliance issues by administering methotrexate parenterally. The importance of these pharmacokinetic issues in adults is less well defined. 

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