Population Pharmacokinetics of Fluconazole in the Treatment of Neonatal Fungal Infectious Disease

Beijing Chilrens' Hospital

This study is based on the hypothesis that the pharmacokinetics of fluconazole in newborns and children are different from adults. We aim to study the population pharmacokinetics of newborns and children receiving the fluconazole for treatment of infectious diseases. In this study, we will detect fluconazole concentration in plasma by using residual blood samples of blood gas analysis and other clinical tests and employ computers for constructing population pharmacokinetic models. In addition, we also want to correlate use of fluconazole with treatment effectiveness and incidence of adverse effects in newborns and children. This novel knowledge will allow better and more rational approaches to the treatment of infectious diseases in newborns and children. It will also set the foundation for further studies to improve fluconazole therapies for newborns and children.

Study Overview

• Status: Recruiting
• Conditions: Pharmacokinetics; Infection; Newborn; Fluconazole
• Intervention / Treatment: Drug: fluconazole

Detailed Description

1. Establish population pharmacokinetic (PPK) models of fluconazole in newborns and children by nonlinear mixed effect modeling (NONMEM).

   At different timepoint after fluconazole administration, plasma samples of 50 newborns and children will be collected from neonatal intensive care unit (NICU) and pneumology department for fluconazole. The clinical information includes demography, medication, concentration data, blood biochemical parameters and so on .

   Plasma samples will be tested by high performance liquid chromatography (HPLC). PPK models of fluconazole will be established by NONMEM program. The reliability and stability of the PPK model will be evaluated by 1000 times of Bootstrap procedure and normalized predictive distribution error (NPDE).

2. Evaluation of the clinical feasibility and safety of individualized dosing.

According the results of PPK models, we will use dosages recommended in models to cure children infectious diseases in prospective studies. For fluconazole, 150 newborns and children will be collected.

We will compare the therapeutic effects and safety between newborns and children with conventional therapies and those with individualized therapies, including proportions of newborns and children with effective fluconazole concentration, improvement speed of of newborns and children, liver and kidney functions, adverse reactions of drugs, and so on.

• Study Type: Observational
• Enrollment (Anticipated): 150

Contacts and Locations

• Study Contact: Name: A-Dong Shen, Master; Phone Number: +86-010-59616898; Email: shenad16@hotmail.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100020
      • Recruiting
      • Beijing Children's Hospital of Capital Medical University
      • Contact: Adong Shen, Master; Phone Number: 13370115087; Email: shenad16@hotmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 minute to 4 weeks (Child)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Neonates on fluconazole

Description

Inclusion Criteria:

Newborn （0-28d） with fluconazole against infectious diseases. The anti-infective therapy includes drugs commonly used in children infectious diseases.

Newborns infectious diseases include pneumonia, sepsis, purulent meningitis and other diseases with infection.

Informed consent signed by the parents and/or guardians.

Exclusion Criteria:

1. Allergic to any class of antibiotics;
2. Receiving other experimental drugs;
3. There are other factors that clinicians consider unsuitable for inclusion in the study.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Newborns and children with the usage of fluconazole; Newborn with fluconazole against infectious diseases.	Drug: fluconazole; According to the models of population pharmacokinetics,the investigators and want to correlate use of fluconazole with treatment effectiveness and safety in newborns

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
maximum concentration (Cmax)	Cmax is a term used in pharmacokinetics refers to the maximum (or peak) serum concentration that a drug achieves in a specified compartment or test area of the body after the drug has been administrated and before the administration of a second dose.	up to 4 weeks

Collaborators and Investigators

• Sponsor: Beijing Children's Hospital
• Collaborators: Shandong University
• Investigators: Principal Investigator: A-Dong Shen, Master, Beijing Children's Hospital of Capital Medical University

Publications and helpful links

General Publications

• Jacqz-Aigrain E, Leroux S, Zhao W, van den Anker JN, Sharland M. How to use vancomycin optimally in neonates: remaining questions. Expert Rev Clin Pharmacol. 2015;8(5):635-48. doi: 10.1586/17512433.2015.1060124. Epub 2015 Aug 4.
• Zhao W, Lopez E, Biran V, Durrmeyer X, Fakhoury M, Jacqz-Aigrain E. Vancomycin continuous infusion in neonates: dosing optimisation and therapeutic drug monitoring. Arch Dis Child. 2013 Jun;98(6):449-53. doi: 10.1136/archdischild-2012-302765. Epub 2012 Dec 19.
• Leroux S, Zhao W, Betremieux P, Pladys P, Saliba E, Jacqz-Aigrain E; French Society of Neonatology. Therapeutic guidelines for prescribing antibiotics in neonates should be evidence-based: a French national survey. Arch Dis Child. 2015 Apr;100(4):394-8. doi: 10.1136/archdischild-2014-306873. Epub 2015 Jan 27.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2020
• Primary Completion (Anticipated): October 31, 2023
• Study Completion (Anticipated): December 31, 2023

Study Registration Dates

• First Submitted: March 8, 2023
• First Submitted That Met QC Criteria: March 8, 2023
• First Posted (Actual): March 20, 2023

Study Record Updates

• Last Update Posted (Actual): March 20, 2023
• Last Update Submitted That Met QC Criteria: March 8, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Hormones, Hormone Substitutes, and Hormone Antagonists; Cytochrome P-450 Enzyme Inhibitors; Hormone Antagonists; Antifungal Agents; Steroid Synthesis Inhibitors; 14-alpha Demethylase Inhibitors; Cytochrome P-450 CYP2C9 Inhibitors; Cytochrome P-450 CYP2C19 Inhibitors; Fluconazole
• Other Study ID Numbers: NCT2020

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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