Using a Population Pharmacokinetic Model to Estimate the Dosage of Teicoplanin in Patients With Hematologic Malignancy or Critical Illness

National Taiwan University Hospital Yun_Lin Branch

Model Informed Precision Dosing (MIPD) integrates clinical data to optimize dosing for patients with unstable pharmacokinetics, like those with hematologic malignancies or critical illnesses. This study aims to create a pharmacokinetic model for teicoplanin, addressing complex dosing challenges and improving therapeutic outcomes through MIPD-driven recommendations.

Study Overview

• Status: Not yet recruiting
• Conditions: Critical Illness; Hematological Malignancies
• Intervention / Treatment: Other: concentration of teicoplanin

Detailed Description

In recent years, there has been a trend towards not only monitoring drug concentrations but also incorporating clinically significant data into mathematical models to provide recommended dosages with improvement of clinical treatment outcomes, known as Model Informed Precision Dosing (MIPD). The purpose of MIPD is to address the challenges faced by patients with unstable pharmacokinetics, such as those with hematologic malignancies or critical illnesses. These patients often struggle to achieve stable drug concentrations due to various factors, leading to suboptimal therapeutic effects. Both hematologic malignancy and critically ill patients are prone to infections. Since pathogens are difficult to diagnose early, the primary strategy is to administer broad-spectrum antibiotics that cover Gram-positive bacterial infections. Teicoplanin, a glycopeptide antibiotic, is used to treat infections caused by Gram-positive bacteria, including Staphylococcus aureus. However, due to its long elimination half-life (83~182 hours), It has been a clinical challenge to determine the appropriate dosage. Additionally, these two patient groups often exhibit hypoalbuminemia and unstable renal function. Since teicoplanin is highly protein-bound (90-95% bound) and primarily excreted by the kidneys (97% excretion), optimal dosing recommendations require therapeutic monitoring to achieve better treatment outcomes.

Recommended target of therapeutic drug monitoring was established by the Japanese Society of Infectious Diseases in 2022. The targeted pharmacokinetic pharmacodynamic parameter is the 24 hours area under the curve to minimum inhibitory concentration (AUC24/MIC). Since MIPD software to estimate AUC of teicoplanin is not available in many institutions, achieving the trough level target is recommended. Our previous study found that, following a loading dose regimen of 12 mg/kg/dose every 12 hours for three doses, followed by a fourth dose at the 24th hour, hematologic malignancy patients achieved the best therapeutic effect if the trough level reached ≥18.85 mcg/ml at 48 hours.

This research aims to retrospectively construct a population pharmacokinetic model by using data from hematologic malignancy patients. Moreover, it will prospectively apply MIPD concept to provide optimal clinical dosage recommendations for hematologic malignancy or critically ill patients and subsequently analyzing the outcomes.

• Study Type: Observational
• Enrollment (Estimated): 600

Contacts and Locations

• Study Contact: Name: Li - yu Pharmacist; Phone Number: 886-972655332; Email: y05306@ms1.ylh.gov.tw

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

• Hematologic Malignancy Group: Patients with cancers affecting blood, bone marrow, or lymph nodes, such as leukemia or lymphoma.
• Critical Illness Group: Patients with life-threatening conditions requiring intensive care, often with unstable vital signs or organ dysfunction.

Description

Inclusion Criteria:

• Adult patients aged over 20 diagnosed with hematologic malignancy or critical illness.
• Clinically require teicoplanin for treating fever with suspected Gram-positive bacterial infection for more than 48 hours.

Exclusion Criteria:

• Adult patients without hematologic malignancy or critical illness.
• Patients not using teicoplanin for fever with suspected Gram-positive bacterial infection.
• patients receiving renal dialysis within 48 hours of starting teicoplanin.
• Patients treated with teicoplanin for less than 48 hours.
• Pregnant women.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
use population pharmacokinetics model to find out the risk factors	From enrollment to the end of treatment at last 2 weeks

Collaborators and Investigators

• Sponsor: National Taiwan University Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2025
• Primary Completion (Estimated): September 30, 2025
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: November 3, 2024
• First Submitted That Met QC Criteria: November 3, 2024
• First Posted (Estimated): November 5, 2024

Study Record Updates

• Last Update Posted (Estimated): November 5, 2024
• Last Update Submitted That Met QC Criteria: November 3, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Keywords: teicoplanin; population pharmacokinetic model; Model-Informed Precision Dosing
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Site; Disease Attributes; Hematologic Diseases; Neoplasms; Hematologic Neoplasms; Critical Illness; Anti-Bacterial Agents; Anti-Infective Agents; Teicoplanin
• Other Study ID Numbers: 202406020RIND

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