Population Pharmacokinetics of Teicoplanin and Its Dosing Recommendations for Neutropenic Patients With Augmented Renal Clearance for Hematological Malignancies.

BACKGROUND

Plasma teicoplanin concentrations do not reach the therapeutic range in several patients with hematological malignancies. Nevertheless, the characteristics of the population pharmacokinetic (PPK) models have not been clarified for malignancy. The decrease in the teicoplanin concentration in patients with cancer has been attributed to augmented renal clearance (ARC). It is essential to identify the causative factors of ARC to construct a PPK model to optimize the administration method. The authors aimed to establish a PPK model and develop an appropriate dosing regimen for teicoplanin in patients with hematological malignancies.

METHODS

PPK analysis was performed using therapeutic drug monitoring (TDM) data from 119 patients with hematological malignancies. The developed model was verified by predictive performance.

RESULTS

The covariates affecting systemic clearance were serum creatinine, presence or absence of neutropenia (<500/μL), and body size descriptor. Patients with hematologic malignancies and neutropenia showed a 25% increase in clearance compared with those with a normal neutrophil count. The PPK model was constructed based on the presence or absence of neutropenia. This model allowed the selection of the most appropriate dosage regimen out of those recommended by the TDM guidelines for patients with eGFR of >60 mL/min/1.73 m2. The PPK model predicted a dosing regimen for achieving a 10% improvement in the coverage probability of the target concentration range during the loading and maintenance phases.

CONCLUSIONS

The PPK model may help optimize dose regimens and evaluate dosing methods, using comparative simulations, in patients with hematological malignancies.