Early Trough Prediction Error of Japanese Population Pharmacokinetic Models for Teicoplanin After Loading in Cancer Patients.

BACKGROUND AND

OBJECTIVE

Published Japanese population pharmacokinetic parameter sets are used for teicoplanin dosing, but their accuracy for teicoplanin trough concentrations in patients with cancer is unclear. This study evaluated agreement between a priori predicted and measured teicoplanin trough concentrations after loading in patients with cancer and identified clinical factors associated with prediction error.

METHODS

We retrospectively studied 217 patients with cancer receiving fixed loading (600 mg twice on days 1 and 2 and 600 mg once on day 3) with a day 4 trough measurement. Day 4 trough concentrations were predicted a priori using three Japanese population pharmacokinetic parameter sets. Prediction error was defined as predicted minus measured (mg/l). Multivariable linear regression evaluated associations with febrile neutropenia status and creatinine clearance (CCr).

RESULTS

Mean prediction error ranged from -5.30 to -1.85 mg/l, indicating underprediction. Underprediction was greater in patients without febrile neutropenia (-7.12 to -2.98 mg/l) than in those with febrile neutropenia (-3.21 to -0.54 mg/l). In multivariable models, febrile neutropenia (vs absence) was associated with less negative prediction error (+4.85 to +5.27 mg/l; all P < 0.001). Higher CCr was associated with more negative prediction error (-0.32 to -0.72 mg/l per 10 ml/min; all P < 0.001), indicating greater underprediction at higher CCr.

CONCLUSIONS

Japanese parameter sets underestimated day 4 teicoplanin trough concentrations after loading in patients with cancer, and prediction error differed by febrile neutropenia status after adjustment for CCr. Early trough measurement after loading should therefore be considered when these parameter sets are used.