Pediatric pharmacokinetic considerations and implications for drug dosing

Abstract

Optimizing the dosing of medicines for pediatric patients in routine clinical practice and determining the dose for clinical trials is still a challenging task. Children differ from adults in their response to drugs due to inherent differences in pharmacokinetics and/or pharmacodynamics, and responses may also vary among pediatric patients of different ages. However, the greatest disparities compared to adult pharmacokinetic profiles are observed in children below 2 years of age. The maturation of the liver and the kidneys, as well as the variation in body composition, are considered to be the main sources of pharmacokinetic variability. Hence, besides specific pharmacodynamic features, understanding age-related changes in drug absorption, distribution, and elimination is fundamental for optimizing drug efficacy and avoiding toxicity. This paper summarizes the pharmacokinetic changes throughout the childhood, along with the effect of developmental changes on drug dosage calculation. In clinical practice, age and body weight-based dosing regimens are usually used. In spite of dosing recommendations based on age and/or body weight, variabilities in pharmacokinetics and pharmacodynamic response remain, implying a need to monitor patients and optimize the dosing regimen according to physiological characteristics, disease characteristics and therapy.

Understanding hemoglobin contribution to high-dose methotrexate disposition—population pharmacokinetics in pediatric patients with hematological malignancies

“…The development of the two-compartment model was in line with most previous population analyzes [7,11,12,15,16,19,23,34], although models with one [13] or three compartments have occasionally been reported [17]. The effect of body weight was included at the beginning of modeling process using standard allometric scaling, whereas the effect of maturation was not considered, since only 2 patients were younger than 2 years [35]. After testing the effects of the remaining covariates on CL, only the influence of SECR and HGB was included the final pharmacokinetic model in addition to body weight.…”

Türki̇ye Teksti̇l Sektörü İş Kazalarinin Eği̇li̇m Ve Gelecek Perspekti̇fleri̇, 2011-2020

“…Bu nedenle iş kazaları ciddi bir küresel halk sağlığı sorunudur [2]. Türkiye'de ve dünyada her an iş kazaları, yaralanmalara, can almaya, fiziksel ve psikolojik zarar vermeye ve işçilerin ve ailelerinin kaynaklarını tüketmeye devam etmektedir [3]. Travmatik mesleki yaralanmanın genel insani, sosyal ve finansal bedeli çok büyüktür ve kanser, kardiyovasküler hastalık gibi rahatsızlıkların sağlık sistemine getirdiği yük gün geçtikçe ağırlaşmaktadır [4].…”