Pharmacokinetics in Children - What is Important for Correct Drug Dosage?

Abstract

Under- or overdosage of medication can lead to severe side effects in children. To avoid this, precise knowledge of age-specific liberation, absorption, distribution, metabolism and excretion - LADME for short - is necessary. Absorption can take place intravenously, orally, rectally, intranasally, transdermally or epidurally/caudally and is associated with numerous special features in children, depending on age and route of application. The distribution in children is faster due to more permeable organ barriers between individual organs and must be adapted for hydrophilic and lipophilic drugs to the patient's age as well as their fat and fat-free body parts. Drug biotransformation takes place through Phase I and Phase II reactions, predominantly in the liver and kidneys. The cytochrome P450 (CYP450) enzyme system is the most important system for this and requires dose adjustment for numerous drugs in the first phase of life. Due to immature kidney function, all drugs with high renal clearance have a prolonged duration of action in the first months of life. Biliary excretion is particularly important for substances with a molecular weight of > 500 g/mol and is of limited functionality during the first months of life. The amount of substrate that is eliminated by the liver and kidneys within a defined period of time is known as clearance and is strongly dependent on the substance and age of the child. Reciprocal to this is the elimination half-life, which has to be considered especially with repetitive administration. Only with sufficient experience with pharmacokinetic variations or comedications within the different age groups, a patient-adapted, individually correct dose application is possible. The knowledge of the age-specific pharmacokinetics together with the knowledge of patient-specific peculiarities and comedications allow an individual drug application characterized by heuristics.