Information on drug absorption and disposition in infants and children has increased considerably over the past 2 decades. However, the impact of specific age-related effects on pharmacokinetics, pharmacodynamics, and dose requirements remains poorly understood. Absorption can be affected by the differences in gastric pH and stomach emptying time that have been observed in the pediatric population. Low plasma protein concentrations and a higher body water composition can change drug distribution. Metabolic processes are often immature at birth, which can lead to a reduced clearance and a prolonged half-life for those drugs for which metabolism is a significant mechanism for elimination. Renal excretion is also reduced in neonates due to immature glomerular filtration, tubular secretion, and reabsorption. Limited data are available on the pharmacodynamic behavior of drugs in the pediatric population. Understanding these age effects provide a mechanistic way to identify initial doses for the pediatric population. The various factors that impact pharmacokinetics and pharmacodynamics mature towards adult values at different rates, thus requiring continual modification of drug dose regimens in neonates, infants, and children. In this paper, the age-related changes in drug absorption, distribution, metabolism, and elimination in infants and children are reviewed, and the age-related dosing regimens for this population are discussed.

BACKGROUND: Epidermal growth factor receptor (EGFR) inhibitors frequently result in dermatologic toxicities, including rash, xerosis, pruritus, and paronychia. Although the frequency and severity of these events have been described, their effect on health-related quality of life (QoL) remains poorly understood. By using a dermatology-specific questionnaire, the authors examined the effect of these toxicities on QoL. METHODS: Patients completed the Skindex-16, a questionnaire that measures the effects on 3 domains of QoL: symptoms, emotions, and functioning. The severity of dermatologic toxicities was assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events, version 3.0 (NCI-CTCAE). Correlations of dermatology QoL scores with NCI-CTCAE grade, skin phototype (SPT), sex, age, type of EGFR inhibitor, and cancer type were investigated. RESULTS: Concordant with greater severity of rash grade, there was an increase in median scores for symptoms (P ¼ .0006), emotions (P < .0001), function (P ¼ .001), and overall score (P < .0001). There was an inverse correlation between age and emotions (r ¼ À0.26; P ¼ .03) and overall score (r ¼ À0.25; P ¼ .04). There was a significant difference between patients aged 50 years and patients aged >50 years with regard to symptoms (P ¼ .02), emotions (P ¼ .03), functioning (P ¼ .04), and overall score (P ¼ .02). There were no significant differences between QoL and SPT, sex, treatment type, or cancer type (P > .05). CONCLUSIONS: Toxicities, including rash, xerosis, paronychia, and pruritus, adversely affected QoL, and rash was associated with a QoL greater decrease. Younger patients reported lower overall QoL than older patients who had the same toxicities. The current results support using the NCI-CTCAE as a correlative tool for measuring the effects of rash on dermatology-specific QoL. Cancer 2010;116:3916-23.

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Dermatological reactions associated with sunitinib occur frequently. Evidence-based treatment recommendations are needed in order to maximize quality of life and optimize clinical outcome.

Design: Conveniencesurveyof100Chicago,Illinois,beachgoers aged 18 to 30 years who were age-and sex-matched with Chicago-area residents who participated in randomdigit-dialed telephone interviews in 1988 and 1994. Setting: Lakefront beach on weekday afternoons in July 2007. Main Outcome Measures: Knowledge of melanoma/ skin cancer link with tanning, and limiting tanning to help prevent melanoma/skin cancer; attitude about the appearance of tanned people; and knowledge of relevant information sources; and UV indoor tanning use in the past year. Results: Knowledge of the melanoma/skin cancer link with tanning changed from 1988 (42%) to 1994 (38%) to 2007 (87%). Knowledge of limiting tanning to help prevent melanoma increased from 1988 (25%) to 1994 (77%), but decreased from 1994 to 2007 (67%). This decline in knowledge about limiting tanning was concurrent with an increase in the attitude that having a tan looks better (1994, 69%; 2007, 81%). Use of indoor tanning beds increased from 1988 (1%) to 1994 (26%) and remained at the same level in 2007 (27%). Although physicians, especially dermatologists, were sources of information about tanning (1988, 2%; 1994, 18%; 2007, 31%) and were considered the most trusted source, only 14% of respondents in 1994 and 2007 reported ever talking to a doctor about indoor tanning. Conclusion: Because young adults report that physicians are their most trusted source of information about tanning, a potential opportunity exists for physicians to influence indoor tanning behavior by counseling their patients.