Related Experiment Video

Updated: Dec 16, 2025

Human Liver Microphysiological System for Assessing Drug-Induced Liver Toxicity In Vitro
11:06

Human Liver Microphysiological System for Assessing Drug-Induced Liver Toxicity In Vitro

Published on: January 31, 2022

5.1K

Paediatric population pharmacokinetic modelling to assess hydrocortisone replacement dosing regimens in young

Robin Michelet1, Johanna Melin1,2, Zinnia P Parra-Guillen1,3

  • 1Department of Clinical Pharmacy and Biochemistry, Institute of Pharmacy, Freie Universitaet Berlin, Berlin, Germany.

European Journal of Endocrinology
|July 5, 2020
PubMed

Insights

Accurate hydrocortisone dosing is crucial for children with adrenal insufficiency. This study developed a pharmacokinetic model to optimize dosing regimens, finding current treatments often result in suboptimal cortisol levels.

Area of Science:

  • Pediatric Endocrinology
  • Pharmacokinetics
  • Drug Dosing

Background:

  • Accurate hydrocortisone dosing in pediatric adrenal insufficiency is critical to prevent overtreatment (iatrogenic Cushing's syndrome) and undertreatment (adrenal crisis).
  • Current dosing strategies require refinement to ensure physiological cortisol exposure in children.

Purpose of the Study:

  • To develop a population pharmacokinetic model for hydrocortisone in pediatric patients.
  • To utilize this model to optimize hydrocortisone replacement therapy regimens in children.

Main Methods:

  • A pharmacokinetic study involving 24 children (2 weeks to 6 years) with adrenal insufficiency.
  • Hydrocortisone concentrations were measured using LC-MS/MS to refine an adult pharmacokinetic model into a pediatric population model.
  • Seven different hydrocortisone treatment regimens were simulated using the developed model.

Main Results:

  • The developed pharmacokinetic model demonstrated good predictive performance.
  • Simulations indicated that most tested regimens achieved an appropriate 24-hour area under the curve (AUC0-24h) in children, but not consistently in neonates.
  • Cortisol levels frequently fell outside the normal range, particularly low levels before the next dose, across all age groups.

Conclusions:

  • Current pediatric hydrocortisone regimens (3- or 4-times daily) may achieve target AUC0-24h but often lead to fluctuating cortisol levels.
  • Low pre-dose cortisol levels are common, suggesting suboptimal timing or dosing in many pediatric patients.
  • Further optimization of hydrocortisone replacement therapy is needed to maintain stable physiological cortisol concentrations.
Abstract

More Related Videos

Quantification of the Immunosuppressant Tacrolimus on Dried Blood Spots Using LC-MS/MS08:38

Quantification of the Immunosuppressant Tacrolimus on Dried Blood Spots Using LC-MS/MS

Published on: November 8, 2015

17.3K
Fecal Glucocorticoid Analysis: Non-invasive Adrenal Monitoring in Equids08:02

Fecal Glucocorticoid Analysis: Non-invasive Adrenal Monitoring in Equids

Published on: April 25, 2016

10.0K

Related Concept Videos

Drug Dosing: Infants and Children01:29

Drug Dosing: Infants and Children

Pediatric patient dosages diverge from adults due to disparities in body surface area, total body water, and extracellular fluid per kilogram of body weight. The dosing regimen considers the variations in pharmacokinetics and pharmacology across distinct age groups, encompassing preterm newborns, infants, young children, older children, and adolescents. Calculation of pediatric patient doses is predicated on determining body surface area, which exhibits a superior correlation with the child's...
155
Pharmacokinetics in Pediatric Patients: Drug Excretion01:26

Pharmacokinetics in Pediatric Patients: Drug Excretion

In pediatric medicine, understanding the renal function and drug elimination nuances is crucial for administering safe and effective treatments. Newborns, in particular, display markedly slower renal functions than adults, profoundly affecting how drugs are cleared from their bodies. This slower drug clearance requires clinicians to extend the dosing intervals for many medications to prevent drug accumulation and toxicity while ensuring therapeutic efficacy.One key area where these adjustments...
133
Pharmacokinetics in Pediatric Patients: Drug Distribution01:17

Pharmacokinetics in Pediatric Patients: Drug Distribution

Drug distribution in the pediatric population exhibits unique challenges and considerations due to the physiological differences between children, particularly neonates and infants, and adults. A crucial aspect of pediatric pharmacology is understanding how these differences impact the pharmacokinetics of various drugs, necessitating age-specific dosing strategies to ensure efficacy and safety.Neonates and infants have a higher total body water content, ~75%–90% of their body weight,...
178
Pharmacokinetics in Pediatric Patients: Drug Metabolism01:24

Pharmacokinetics in Pediatric Patients: Drug Metabolism

In pediatric care, understanding the nuances of hepatic drug metabolism is crucial, as it significantly differs from that of adults. This divergence is primarily due to the developmental stage of drug-metabolizing enzymes, which affects how medications are processed in the body. In neonates, for instance, the activity of Phase I enzymes—critical for the initial breakdown of drugs—is markedly reduced, functioning at just 20–40% of the levels seen in adults. This reduction poses...
115
Pharmacokinetics in Pediatric Patients: Overview and Drug Absorption01:23

Pharmacokinetics in Pediatric Patients: Overview and Drug Absorption

Understanding the physiological differences in the pediatric population is crucial for effective pharmacotherapy. Neonates, infants, and children exhibit significant variations in gastric pH, gastric emptying time, intestinal transit time, and biliary function. These variations profoundly affect oral drug absorption, necessitating a nuanced approach to pediatric dosing.Neonates present with a unique physiological profile, having a gastric pH greater than 4 and faster and more irregular gastric...
149
Dosage Regimens: Partial Pharmacokinetic Parameters01:01

Dosage Regimens: Partial Pharmacokinetic Parameters

It is not uncommon for complete drug pharmacokinetic profiles to remain elusive in pharmacokinetics. This necessitates certain educated assumptions by pharmacokineticists to determine appropriate dosage regimens without comprehensive pharmacokinetic data from animal or human studies. One prevalent assumption is setting the bioavailability factor, denoted as F, to 1 or 100%. This assumption caters to the scenario where a drug doesn't achieve full systemic absorption, resulting in the patient...
83