Related Experiment Video

Updated: Jun 19, 2026

Pre-clinical Evaluation of Tyrosine Kinase Inhibitors for Treatment of Acute Leukemia
10:49

Pre-clinical Evaluation of Tyrosine Kinase Inhibitors for Treatment of Acute Leukemia

Published on: September 18, 2013

18.1K

Fixed dosing of alpelisib for children with vascular anomalies: Can we do better?

Amandine Remy1,2, Albert Etingin3, Paul Gavra4

  • 1General Pediatric Fellowship Program, Sainte-Justine University Hospital, Université de Montréal, Montreal, Canada.

British Journal of Clinical Pharmacology
|January 24, 2025
PubMed

Insights

Alpelisib dosing for severe vascular malformations in children shows high variability. Pharmacokinetic data is crucial for safe and effective treatment, as current fixed doses are weight-independent.

Area of Science:

  • Pharmacology
  • Genetics
  • Pediatrics

Background:

  • Severe vascular malformations (VM) significantly impair quality of life and can cause organ dysfunction.
  • Somatic activating mutations in the PI3K/AKT/mTOR pathway are common in VM.
  • Alpelisib, a PIK3CA inhibitor, is FDA-approved for PIK3CA-related overgrowth syndrome (PROS) in children.

Purpose of the Study:

  • To report novel alpelisib pharmacokinetic (PK) data in pediatric patients with severe VM.
  • To provide data supporting informed alpelisib dosing decisions in children.
  • To address the lack of PK data for the current weight-independent fixed dose.

Main Methods:

  • Nine pediatric patients with severe VM (4 PROS, 5 other VM) were included.
  • Alpelisib was administered at a fixed dose of 50 mg/day.
  • Area under the curve (AUC) was measured to assess drug exposure.

Main Results:

  • Alpelisib AUC demonstrated high variability (CV = 58%) in pediatric patients.
  • Mean age was 10.5 years and mean weight was 43 kg.
  • AUC showed a correlation with patient weight.

Conclusions:

  • The fixed 50 mg/day dose of alpelisib results in highly variable drug exposure in children.
  • Weight-based dosing is urgently needed due to unknown short- and long-term adverse effects.
  • Further PK studies are essential for optimizing alpelisib treatment in pediatric VM.

Keywords:
childrendrug utilizationpharmacokineticstherapeutic drug monitoringvascular anomaliesvascular disease

More Related Videos

Proton Therapy Delivery and Its Clinical Application in Select Solid Tumor Malignancies08:34

Proton Therapy Delivery and Its Clinical Application in Select Solid Tumor Malignancies

Published on: February 6, 2019

20.2K
A Patient-Derived Xenograft Model for Venous Malformation06:51

A Patient-Derived Xenograft Model for Venous Malformation

Published on: June 15, 2020

5.3K

Related Concept Videos

Combination Therapies and Personalized Medicine02:50

Combination Therapies and Personalized Medicine

Combining two or more treatment methods increases the life span of cancer patients while reducing damage to vital organs or tissue from the overuse of a single treatment. Combination therapy also targets different cancer-inducing pathways, thus reducing the chances of developing resistance to treatment.
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
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...
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...
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, compared...
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 a challenge in...
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...