小児の生理・生化学的発達と薬物消失経路を考慮した新たな小児薬用量推定法

Abstract

Conventional dose estimation methods do not consider drug factors and do not allow for various pharmacokinetic factors associated with the growth of children. I have therefore established a new method based on drug elimination processes and physiological and biochemical developmental factors in order to more appropriately estimate pediatric doses (the ePPBD method). Renal excretion or hepatic metabolic clearance was calculated for each age based on physiological and biochemical developmental factors, such as the unbound fraction of the drug in plasma, glomerular filtration rate, tubular secretion, liver volume, and CYP enzyme activity. Then the pediatric dose was estimated by multiplying the adult dose by the pediatric/adult ratio of renal excretion or hepatic metabolic clearance. Accuracy of the ePPBD method was compared with conventional methods, using the population mean clearance and the doses listed in package inserts and text books as the standards to quantitate its validity. In brief, accuracy was evaluated by classifying children into the following age groups: 1) neonates in consideration of the post-conceptional age (PCA), 2) infants up to 2 years old, and 3) children over 2 years old for drugs with renal excretion, or 4) children of all ages for drugs with hepatic metabolism. The accuracy of the ePPBD method was superior to that of conventional methods both for drugs with renal excretion and those with hepatic metabolism, and therefore it should be useful for pediatric patients in whom physiological function changes remarkably as they age.