This study pools published data to describe the increase in glomerular filtration rate (GFR) from very premature neonates to young adults. The data comprises measured GFR (using polyfructose, (51)Cr-EDTA, mannitol or iohexol) from eight studies (n = 923) and involved very premature neonates (22 weeks postmenstrual age) to adulthood (31 years). A nonlinear mixed effects approach (NONMEM) was used to examine the influences of size and maturation on renal function. Size was the primary covariate, and GFR was standardized for a body weight of 70 kg using an allometric power model. Postmenstrual age (PMA) was a better descriptor of maturational changes than postnatal age (PNA). A sigmoid hyperbolic model described the nonlinear relationship between GFR maturation and PMA. Assuming an allometric coefficient of 3/4, the fully mature (adult) GFR is predicted to be 121.2 mL/min per 70 kg [95% confidence interval (CI) 117-125]. Half of the adult value is reached at 47.7 post-menstrual weeks (95%CI 45.1-50.5), with a Hill coefficient of 3.40 (95%CI 3.03-3.80). At 1-year postnatal age, the GFR is predicted to be 90% of the adult GFR. Glomerular filtration rate can be predicted with a consistent relationship from early prematurity to adulthood. We propose that this offers a clinically useful definition of renal function in children and young adults that is independent of the predictable changes associated with age and size.

Purpose: The aim of this study was to define the pharmacokinetics of carboplatin in children and use the data to develop a pediatric dose formula. It was anticipated that renal function would be a major determinant of carboplatin disposition and the relationship between carboplatin clearance and glomerular filtration rate (GFR) was examined in detail.Patients and Methods: Plasma carboplatin pharmacokinetics were measured as ultrafiltrable platinum in 22 patients (5 to 63 kg) following 200 to 1,000 mg/m2 of carboplatin. GFR was measured by the plasma clearance of chromium 51-edathamil ( treatment of neuroblastoma, pediatric brain tumors, and germ cell tumors, and the use of the drug in these diseases is increasing.'3 Studies in adults have shown that the pharmacokinetics of carboplatin have a major impact on the toxicity of the drug and also, probably, on its activity. Thus, a number of investigations have shown a relationship between carboplatin exposure, expressed as the area under the plasma carboplatin concentration versus time curve (AUC), and tolerance to the drug, in particular thrombocytopenia. 6The work reported by Horwich et al 7 with testicular teratoma patients suggests that inadequate carboplatin exposure (AUC < 4 mg/mL-min) may compromise activity in this chemotherapy-curable disease. Similarly, a retrospective analysis reported by Jodrell et al 8 implied that ovarian cancer patients who received carboplatin at doses calculated to have produced AUC values less than 4 mg/ mL* min were less likely to achieve a response than those calculated to have experienced exposures greater than 4 mg/mL, min. Finally, preliminary results from a randomized study in ovarian cancer of an AUC of 6 mg/ mL* min administered every 4 weeks for six courses vs an AUC of 12 mg/mL-min administered every 4 weeks for four courses, suggests that the complete response rate is higher in the high AUC arm. 9In adults, for a given surface area-based dose of carboplatin, the AUC achieved varies over a twofold to

A number of initiatives have curtailed anthropogenic mercury emissions in North America over the last two decades; however, various factors, including long-range transport of global emissions, may complicate the response of fish mercury levels to remedial actions. Since the Great Lakes of North America are together the largest surface freshwater body in the world and are under the influence of many complicating factors, trends of mercury in fish from the Great Lakes can reflect the overall impact of mercury management actions at local, regional, and perhaps global scales. Here we present a comprehensive view of mercury trends in Canadian Great Lakes fish using two large (total 5807 samples), different (fillet and whole fish), and long-term (1970s-2007) monitoring data sets. The spatial differences in lake trout and walleye mercury levels during this period have generally been within a factor of 2-3 with Lakes Erie and Superior having the lowest and highest concentrations, respectively. These spatial differences have diminished in the recent years (2000-2007). The concentrations have generally declined over the three decades (mid-1970s to 2007); however, in recent years, the concentration trends are flat in Lake Ontario walleye and appear to be increasing in Lake Erie walleye. There was a mismatch in the Lake Ontario lake trout and walleye temporal trends, which shows the importance of considering more than one fish species for proper spatial/temporal trend assessments.

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