Variability in Trough Total and Unbound Teicoplanin Concentrations and Achievement of Therapeutic Drug Monitoring Targets in Adult Patients with Hematological Malignancy

Abstract

The objective of this study was to explore the following aspects of teicoplanin use in patients with hematological malignancy: early attainment of target trough concentrations with current high-dose teicoplanin regimens, variability in unbound teicoplanin fractions, factors associated with observed total and unbound trough concentrations, efficacy and toxicity, and renal function estimation. This was a single-center, prospective study. Samples for determination of trough concentrations were taken on days 3, 4, 7, and 10. Total and unbound teicoplanin concentrations were determined using validated high-performance liquid chromatography methods. Regression analyses were used to identify the factors associated with the trough concentration. Thirty teicoplanin-treated adults with hematological malignancy were recruited. Despite the use of dosages higher than the conventional dosages, the proportions of patients with a trough concentration of Ն20 mg/liter at 48 h and at 72 h were 16.7% and 37.9%, respectively. Renal function was significantly negatively associated with total trough concentrations at 48 h and 72 h (P Ͻ 0.05). For an average hematological malignancy patient (creatinine clearance ϭ 70 ml/ min), sequential loading doses of at least 12 mg/kg of body weight may be needed to achieve early adequate exposure. In the absence of measured creatinine clearance, estimates obtained using the Cockcroft-Gault (total body weight) equation could prove to be an acceptable surrogate. The unbound fractions of teicoplanin were highly variable (3.4 to 18.8%). Higher unbound fractions were observed in patients with low serum albumin concentrations. Teicoplanin was well tolerated. Teicoplanin loading doses higher than those in current use appear to be necessary. Increased dosing is needed in patients with increased renal function. The high variability in protein binding supports the contention for therapeutic drug monitoring of unbound teicoplanin concentrations. (This study has been registered with EudraCT under registration no. 2013-004535-72.)

Retrospective analysis of relationships among the dose regimen, trough concentration, efficacy, and safety of teicoplanin in Chinese patients with moderate–severe Gram-positive infections

“…This is consistent with previous research. 9 , 14 , 15 , 17 , 20 , 21 , 23 , 27 , 29 All patients were divided into groups based on Cl cr and loading regimens. As a result, ratios of the 3-day loading dose to Cl cr and C min were significantly correlated ( R =0.59, P <0.001; Figure 4 ).…”

Clinical efficacy and safety in patients treated with teicoplanin with a target trough concentration of 20 μg/mL using a regimen of 12 mg/kg for five doses within the initial 3 days

“…On the basis of a PK study of healthy volunteers, multiple-dose teicoplanin administration from 3 to 12 mg/kg of body weight showed a linear dose-serum concentration relationship [21]. However, the dose-serum concentration in critically ill patients can be highly variable [22][23][24]. Serum albumin concentrations are an important determinant of PK for antibiotics that have a high binding affinity to albumin such as teicoplanin.…”

Therapeutic Drug Level Monitoring of Teicoplanin in Korean Pediatric Patients with Normal versus Impaired Renal Function

“…Pharmacokinetics of teicoplanin has been steadily studied in various clinical settings, including adult patients, 5 10 11 12 13 pediatric patients, 14 15 16 17 18 19 20 and patients with hematologic malignancies. 21 22 23 24 25 A number of studies on the pharmacokinetics of teicoplanin have shown a common problem that the therapeutic range of trough level is not achieved early and occasionally not reached even at steady state. To overcome this problem, the need of loading dose has been suggested.…”