Pharmacometric Modeling of a Hospital Preparation (PEDIATENS)

Pharmacometric Modeling of a Hospital Preparation of Nicardipine Hydrochloride Oral Solution at 2 mg/mL in Hypertensive Patients in Pediatric Hematology-oncology

Pediatric prescribers are very often faced with a lack of suitable therapies, particularly oral ones. This represents a major public health problem and necessitates adjustments to dosage or pharmaceutical form using medications marketed for adults, some of which contain excipients that may be harmful to children. This creates risks of dilution errors, administration errors, and the occurrence of adverse effects. Hospital pharmacy technicians are called upon daily to provide appropriate treatment for children. However, although this activity is authorized (Public Health Code, Good Preparation Practices), pharmacokinetic/pharmacodynamic studies on these preparations are only exceptionally carried out. Indeed, only stability studies are required to determine the expiration date of the preparation. Thus, prescribers are left without the necessary information to choose the dosage and administration schedule. Pediatric dosages are extrapolated from those for adults without any certainty of the treatment's effectiveness.

Study Overview

• Status: Not yet recruiting
• Conditions: Hypertensive Patients
• Intervention / Treatment: Other: Evaluation of the pharmacokinetic parameters of an oral formulation of nicardipine hydrochloride

Detailed Description

The pediatric hematology-oncology department wanted to include an oral form of nicardipine in its therapeutic arsenal. Nicardipine is a widely used antihypertensive drug for secondary hypertension, particularly that caused by corticosteroid use. This oral form is preferred for its flexibility in dosing, which is based on weight and blood pressure readings. A first formulation was developed in 2017 and subsequently optimized in terms of excipients and raw material availability, leading to a second formulation in 2021. Nicardipine oral solution has been routinely prepared, dispensed, and administered for many years. The lack of bibliographic data concerning the use of nicardipine in a pediatric population prevents us from understanding the pharmacokinetic (PK) parameters, which are nevertheless essential for optimizing the benefit/risk balance of the drug and for individualizing doses. This study aims to optimize the use of this preparation in the management of hypertension in pediatrics and to promote the benefits of this formulation. This study is valuable because it is situated within the context of the routine therapeutic management of a patient in the pediatric hematology-oncology department suffering from hypertension. It therefore does not entail any modification of the child's care.

• Study Type: Observational
• Enrollment (Estimated): 30

Contacts and Locations

• Study Contact: Name: vincent VF FERRANTI, ARC; Phone Number: +33 02 32 88 82 65; Email: Vincent.Ferranti@chu-rouen.fr
• Study Contact Backup: Name: Delphine DP PICOCHE, Director; Phone Number: +33 02 32 88 82 65; Email: delphine.picoche@chu-rouen.fr

Study Locations

• France
  • Rouen, France, 76031
    • University Rouen Hospital
    • Contact: Thomas TD DUFLOT, Doctor; Phone Number: +33 02 32 88 56 34; Email: thomas.duflot@chu-rouen.fr
    • Contact: Marine MC CAVELIER, Doctor; Phone Number: +33 02 32 88 19 26; Email: marine.cavelier@chu-rouen.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Children in pediatric hematology-oncology requiring nicardipine administration as part of their standard care whether or not they are nicardipine-naïve (switching from the intravenous form used for hypertensive emergencies to the oral form, or patients already receiving hospital-prepared nicardipine oral solution at 2 mg/mL)

Description

Inclusion Criteria:

• Patients aged 1 to 15 years, male or female.
• Patients followed in pediatric hematology-oncology.
• Patients with a central venous catheter as part of their initial care and available for blood sampling.
• Patients with a prescription for oral nicardipine (oral solution) whose formulation and/or dosage is/are not compatible with the commercial form of Loxen® 20 mg, requiring preparation.
• Patients requiring oral administration of nicardipine every 8 hours (initial prescription or renewal).
• Patients covered by a social security scheme.
• Parents/guardians informed of the study and not objecting to their child's participation
• For minors old enough to understand: patients who have not objected to the research.

Exclusion Criteria:

• Patient n'ayant pas un schéma d'administration toutes les 8 heures.
• Hypersensibilité à la substance active.
• Antécédent d'allergie à l'un des excipients (polysorbate 80, hypromellose, saccharine sodique, sorbate de potassium, acide citrique, citrate de sodium, saccharose).
• Refus de participation de l'enfant, des parents ou du représentant légal.
• Inclusion de l'enfant dans un autre essai clinique, si des prélèvements sanguins supplémentaires sont également prévus, dans un délai de 7 jours.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetic parameters in the target population of an oral formulation of nicardipine hydrochloride prepared by the pharmaceutical technology unit of the pharmacy at the Rouen University Hospital (Area Under the Curve (AUC)).	This kinetic profile will be obtained through modeling using Monolix® software and the results of validated assays of the samples. A small blood volume (1 mL) is required for these samples, which are taken from children who previously had a central venous catheter inserted.	24 hours
Pharmacokinetic parameters in the target population of an oral formulation of nicardipine hydrochloride prepared by the pharmaceutical technology unit of the pharmacy at the Rouen University Hospital (apparent distribution volume (Vd/F)).	This kinetic profile will be obtained through modeling using Monolix® software and the results of validated assays of the samples. A small blood volume (1 mL) is required for these samples, which are taken from children who previously had a central venous catheter inserted.	24 hours
Pharmacokinetic parameters in the target population of an oral formulation of nicardipine hydrochloride prepared by the pharmaceutical technology unit of the pharmacy at the Rouen University Hospital (apparent clearance (Cl/F)).	This kinetic profile will be obtained through modeling using Monolix® software and the results of validated assays of the samples. A small blood volume (1 mL) is required for these samples, which are taken from children who previously had a central venous catheter inserted.	24 hours
Pharmacokinetic parameters in the target population of an oral formulation of nicardipine hydrochloride prepared by the pharmaceutical technology unit of the pharmacy at the Rouen University Hospital (maximum concentration (Cmax)).	This kinetic profile will be obtained through modeling using Monolix® software and the results of validated assays of the samples. A small blood volume (1 mL) is required for these samples, which are taken from children who previously had a central venous catheter inserted.	24 hours
Pharmacokinetic parameters in the target population of an oral formulation of nicardipine hydrochloride prepared by the pharmaceutical technology unit of the pharmacy at the Rouen University Hospital (time to reach this concentration (Tmax)).	This kinetic profile will be obtained through modeling using Monolix® software and the results of validated assays of the samples. A small blood volume (1 mL) is required for these samples, which are taken from children who previously had a central venous catheter inserted.	24 hours
Pharmacokinetic parameters in the target population of an oral formulation of nicardipine hydrochloride prepared by the pharmaceutical technology unit of the pharmacy at the Rouen University Hospital (elimination constant (ke)).	This kinetic profile will be obtained through modeling using Monolix® software and the results of validated assays of the samples. A small blood volume (1 mL) is required for these samples, which are taken from children who previously had a central venous catheter inserted.	24 hours
Pharmacokinetic parameters in the target population of an oral formulation of nicardipine hydrochloride prepared by the pharmaceutical technology unit of the pharmacy at the Rouen University Hospital (elimination half-life (t1/2)).	This kinetic profile will be obtained through modeling using Monolix® software and the results of validated assays of the samples. A small blood volume (1 mL) is required for these samples, which are taken from children who previously had a central venous catheter inserted.	24 hours
Pharmacokinetic parameters in the target population of an oral formulation of nicardipine hydrochloride prepared by the pharmaceutical technology unit of the pharmacy at the Rouen University Hospital (clairance inter-compartimentale apparente (Q/F)).	This kinetic profile will be obtained through modeling using Monolix® software and the results of validated assays of the samples. A small blood volume (1 mL) is required for these samples, which are taken from children who previously had a central venous catheter inserted.	24 hours
Pharmacokinetic parameters in the target population of an oral formulation of nicardipine hydrochloride prepared by the pharmaceutical technology unit of the pharmacy at the Rouen University Hospital (apparent central volume (Vc/F)).	This kinetic profile will be obtained through modeling using Monolix® software and the results of validated assays of the samples. A small blood volume (1 mL) is required for these samples, which are taken from children who previously had a central venous catheter inserted.	24 hours
Pharmacokinetic parameters in the target population of an oral formulation of nicardipine hydrochloride prepared by the pharmaceutical technology unit of the pharmacy at the Rouen University Hospital (apparent peripheral volume (Vp/F)).	This kinetic profile will be obtained through modeling using Monolix® software and the results of validated assays of the samples. A small blood volume (1 mL) is required for these samples, which are taken from children who previously had a central venous catheter inserted.	24 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Describe the distribution of the residual concentration at 24 hours	Evaluate the determination of the residual concentration of nicardipine hydrochloride at 24 hours.	24 hours
Demographic parameters of the studied population: sex	Evaluate the demographic parameters of the studied population: sex	24 hours
Demographic parameters of the studied population: age	Evaluate the demographic parameters of the studied population: age	24 hours
Demographic parameters of the studied population: weight .	Evaluate the demographic parameters of the studied population: weight.	24 hours
Demographic parameters of the studied population: height.	Evaluate the demographic parameters of the studied population : height.	24 hours
Dosages of the studied population: dose/kg/8 hours.	Collection and measurement of prescribed nicardipine dosages: dose/kg/8 hours	24 hours
A mathematical model capable of predicting, through simulation, exposure to and the antihypertensive effects of nicardipine in this population.	Measurement of blood pressure (systolic and diastolic) and heart rate using a monitor to propose a mathematical model of pharmacodynamic parameters	24 hours
Tolerance to treatment	Collection of adverse events reported to the Regional Pharmacovigilance Centre (CRPV) in the context of routine practice	24 hours
Acceptability of treatment	The acceptability of the oral solution (in the form of a visual analog scale) will be assessed at each of the 3 doses	24 hours

Collaborators and Investigators

• Sponsor: University Hospital, Rouen
• Investigators: Study Director: Marine MC CAVELIER, Doctor, University Rouen Hospital; Study Chair: Thomas TD DUFLOT, Doctor, University Rouen Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): March 1, 2026
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): June 1, 2028

Study Registration Dates

• First Submitted: January 19, 2026
• First Submitted That Met QC Criteria: January 19, 2026
• First Posted (Actual): January 28, 2026

Study Record Updates

• Last Update Posted (Actual): January 28, 2026
• Last Update Submitted That Met QC Criteria: January 19, 2026
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: Pharmacometric modeling; hématologie-oncologie pédiatrique
• Other Study ID Numbers: 2022/0354/OB; N° IDRCB : 2025-A01969-40 (Other Identifier: ANSM)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: The data provided will be the property of the sponsor and will be used solely for its own research activities.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No