![]() ![]() Data of gadobutrol 4 and gadoterate 5 were collected from their clinical pharmacology reviews, in which SCR was analyzed using IDMS-traceable Jaffe and enzymatic methods for pediatric patients without renal impairment. 2, 3 The PK data of gadobutrol, gadoterate, amikacin and vancomycin were measured in the time frames of 2007 – 2013, 2015 – 2015, 2001 – 2016, and 2006 – 2016, respectively. ![]() All four drugs were administered intravenously as previously described. Gadobutrol, gadoterate, amikacin, and vancomycin were selected as model drugs since they are predominantly (>90%) eliminated by renal glomerular filtration with minimal tubular secretion/reabsorption. Additionally, the predictive performance of these formulas on CL in pediatrics is unknown, especially in the first 2 years of life when renal function may not be fully mature. These equations have been applied either as a continuous variable to calculate dosage directly, or as a categorical variable to adjust the dose for pediatric patients ( Table 1). Based on our survey of U.S Food and Drug Administration (FDA)-approved drug labeling, 1 the Schwartz equations have been used for guiding dose adjustment for pediatric patients with renal impairment ( Table 1). Those equations are potential predictors of renal drug clearance, which could inform dose selection of drugs that are predominantly renally eliminated. Various equations have been developed to obtain the estimated glomerular filtration rate (eGFR) as a measure of renal function based on serum creatinine (SCR), cystatin C, and other biomarkers. Drug clearance (CL) is a critical parameter for selecting an age-appropriate dose and is often predicted by developmental changes in renal and hepatic function. In pediatric drug development, an initial dose needs to be proposed before starting a clinical trial. When greater precision is required in predicting eGFR for pediatric patients, such as in drug dosing, revised k constants for the Schwartz equation or new methods of GFR estimation may be necessary.ĭose selection is challenging for pediatric patients due to the dynamic changes in drug pharmacokinetics and pharmacodynamics related to physiological growth, maturation, and organ function. In conclusion, Schwartz equations led to an overestimation of drug clearance for the drugs evaluated. Excluding the subjects with supraphysiological eGFR from the analysis did not change the overall trend of overestimation. Supraphysiological eGFR as high as 380 mL/min/1.73m 2 was obtained using bedside Schwartz equation for some of the subjects, most of whom are children less than two years of age with SCR < 0.2 mg/dL. Further analysis with bedside Schwartz equation showed a higher eGFR/CL ratio in the subjects with a lower SCR or CL. Multiple eGFR equations overestimated the drug clearance on average, including the original and bedside Schwartz equations, which showed an average eGFR/CL ratio between 1 and 3. ![]() The eGFR was compared with the observed drug clearance (CL) in 352 pediatric patients from birth to 12 years of age. This study evaluated the performance of those equations in estimating individual clearance of drugs that are predominantly eliminated by glomerular filtration, using clinical data from the renally-eliminated drugs gadobutrol, gadoterate, amikacin, and vancomycin. The estimated glomerular filtration rate (eGFR) equations based on serum creatinine (SCR) have been used for pediatric dose adjustment in drug labeling. ![]()
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |