My child is unique; the pharmacokinetics are universal

Abstract

The pharmacokinetic (PK) parameters that are important for dosing (e.g., clearance and volume) are well known. They are used in universal mathematical formulae that describe the time course of drug concentration. Additional formulae can be used to describe major covariate effects in children, such as size and maturation. PK parameters describing the time-concentration profile of a drug after administration are those for a typical individual in a population. These parameters are associated with variability. Further, any one individual may not be typical of the population studied. While size and maturation are two important considerations in children and assist with dosing estimation, there are also a number of additional PK covariates (e.g., organ function, disease, drug interactions, pharmacogenetics), and identifying these sources of variability allows us to individualize drug dose. Pharmacology is not simply an application of PK, and determinants of drug dose also require an understanding of the variability associated with pharmacodynamic response and a balancing of beneficial effects against unwanted effects. Each child is unique in this respect.

Guidelines for Monitoring and Management of Pediatric Patients Before, During, and After Sedation for Diagnostic and Therapeutic Procedures: Update 2016

“…The practitioner should consult various sources (a pharmacist, textbooks, online services, or handheld databases) for specific information on drug interactions. [315][316][317][318][319] The US Food and Drug Administration issued a warning in February 2013 regarding the use of codeine for postoperative pain management in children undergoing tonsillectomy, particularly those with OSA. The safety issue is that some children have duplicated cytochromes that allow greater than expected conversion of the prodrug codeine to morphine, thus resulting in potential overdose; codeine should be avoided for postprocedure analgesia.…”

Infant spinal anesthesia: Do girls need a larger dose of local anesthetic?

“…During infancy and up to the first year of life, there are important age‐dependent changes in body composition, weight, and maturation of hepatic and renal function resulting in extensive interindividual variability of drug disposition . Maturational pharmacokinetics describe the changes in drug absorption, distribution, metabolism, and elimination, while maturational pharmacodynamics describe changes in the concentration effect profile (differences in receptor expression, function, or specific tissue/organ sensitivity).…”

Pharmacotherapy during pediatric extracorporeal membrane oxygenation: a review

“…Recent advances in separation methods, such as high-performance liquid chromatography (HPLC) and ultra high-performance liquid chromatography (UHPLC), along with mass spectrometry (MS) detection methods allow for very sensitive analysis of small sample volumes [110,111]. The collection of high quality PK data, even using non-traditional techniques, allows for the generation of population PK and population PKPD models as well as potentially physiologically-based pharmacokinetic (PBPK) models and clinical trials simulations (CTS) that, with the appropriate validation procedures, can be more broadly applicable and allow for extrapolation to multiple drugs or patient scenarios [112][113][114][115][116][117]. Researchers should focus on drugs that do not have TDM widely available, those at high risk for drug-drug interactions, and those that cannot be actively titrated to effect by clinicians at the bedside.…”