Handling of drugs in children with abnormal renal function

Abstract

Every pediatrician must be able to administer the correct dosage for a variety of drugs across a wide array of patients: from a prematurely born baby weighing only 500 g to a large adolescent whose weight may exceed 120 kg. As a result, knowledge concerning changes in drug disposition as a result of childhood development is extremely important. An exceptional outline of the many changes that occur during human development that may alter drug disposition was published by Kearns et al. [1]. The changes his team listed include (i) changes in the integumentary development; (ii) changes in the volume of distribution (newborns have the highest total body water volume); (iii) changes in gastrointestinal function, hydrochloric acid production, and bile acid excretion; (iv) changes in the metabolic capacity of key enzymes; and, of course, (v) the acquisition of renal function. The effect of these changes can be so profound that an infant may metabolize a drug ten times faster than an adult and may form completely different metabolites. A study conducted by our team recently demonstrated such a disparity in the way that sirolimus is metabolized, finding a half-life of 72 h in adults and a half-life as short as 7 h in young children [2]. Moreover, the metabolite patterns in both groups were diametrically different [3].