Therapeutic Drug Monitoring of Teicoplanin in Haematological Malignancy Patients with Febrile Neutropenia and Optimizing Dosage Regimens.

Abstract

This study used high-performance liquid chromatography to measure 202 teicoplanin plasma trough concentrations (Cmin ) in 114 haematological malignancy patients with febrile neutropenia. Patients were divided into two groups according to the mean initial dose (MID) over the first 3 days of treatment: (i) MID = 533.33 mg/day (loading dose group, 400 mg q12h for three doses followed by 400 mg qd, n = 62) and (ii) MID < 533.33 mg/day (unloaded or underloaded group, n = 52). During the first 3 days after treatment, the overall Cmin was higher in group 1 than in group 2 (10.96 ± 5.44 mg/L versus 6.31 ± 3.73 mg/L, mean ± S.D.; p = 0.002), as was the qualifying rate of Cmin > 10 mg/L (54.5% versus 11.1%, p = 0.001), and the probability of Cmin < 5 mg/L was lower in group 1 than in group 2 (13.6% versus 40.7%, p = 0.037). After 3 days, the average Cmin and qualifying rates did not differ significantly between the two groups, and the average Cmin was <10 mg/L in both groups. Binary logistic regression analysis revealed that creatinine clearance (p = 0.004) and MID (p = 0.010) could affect Cmin during the first 3 days of treatment and that age (p = 0.022) only could affect Cmin after 3 days. In conclusion, it is necessary to apply loading dose to achieve teicoplanin Cmin > 10 mg/L rapidly and, from a pharmacokinetic/pharmacodynamic perspective, 600 mg is recommended as loading and maintenance dose for these patients when AUC24 /minimum inhibitory concentration > 345.