Population Pharmacokinetics and Model-Informed Dose Optimization of Teicoplanin in Adults with Hematological Malignancies

TL;DR

This study develops a model to optimize teicoplanin dosing in cancer patients to ensure effective drug levels.

Contribution

A population pharmacokinetic model and individualized dosing strategies for teicoplanin in hematological malignancy patients.

Findings

Ideal body weight, age, and kidney function significantly affect teicoplanin clearance.

Standard dosing regimens fail to achieve therapeutic concentrations in some patients.

An intensified regimen with five loading doses achieves optimal drug levels in most patients.

Abstract

Background: Teicoplanin is widely used for the empirical and targeted treatment of febrile neutropenia in patients with hematological malignancies. However, the pathophysiological alterations typical of this population may substantially affect drug exposure. The aim of this study was to develop and validate a population pharmacokinetic (PopPK) model of teicoplanin in adult hematological patients and to propose individualized dosing strategies. Methods: A retrospective, single-center study including 151 patients and 263 serum concentrations was conducted, with participants assigned to development (n = 100) and validation (n = 51) cohorts. Concentrations were quantified using a turbidimetric immunoassay, and the PopPK model was developed in NONMEM using FOCE-I. Results: Teicoplanin pharmacokinetics were described by a one-compartment model with first-order elimination. Ideal body weight, estimated glomerular filtration rate, and age were identified as significant predictors of clearance. Internal and external validation confirmed the robustness and predictive performance of the model. Monte Carlo simulations showed that conventional regimens (6 mg/kg every 12 h for three loading doses, followed by 6 mg/kg once-daily, or 600 mg every 12 h for three loading doses, followed by 600 mg once-daily) are insufficient to achieve therapeutic trough concentrations (≥15–20 mg/L) within the first 72 h, particularly in patients with preserved renal function or higher body weight. An intensified regimen consisting of five loading doses of 12 mg/kg every 12 h, followed by 12 mg/kg once-daily, enabled rapid attainment and maintenance of trough concentrations ≥ 20 mg/L in patients with lower to intermediate ideal body weight. Conclusions: These findings underscore the importance of intensified dosing strategies and covariate-guided individualization supported by therapeutic drug monitoring to achieve optimal teicoplanin exposure in this vulnerable patient group.

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