Variability in Teicoplanin Protein Binding and Its Prediction Using Serum Albumin Concentrations

Abstract

The impact of lower serum albumin levels on teicoplanin pharmacokinetics has not been previously determined. The authors assessed the relationship between total and free concentrations of teicoplanin in serum samples obtained from patients receiving teicoplanin therapy for Gram-positive bacterial infections. In addition, the authors determined the contribution of serum albumin concentrations to the unbound fraction of teicoplanin. One hundred ninety-eight serum samples were obtained from 65 patients undergoing routine therapeutic drug monitoring of teicoplanin. Free serum teicoplanin was separated by ultrafiltration, and total and free serum concentrations of teicoplanin were determined by a fluorescence polarization immunoassay. Regression analysis was then performed to build a prediction model for the free serum teicoplanin concentration from the total serum teicoplanin concentration and the serum albumin level using the first 132 samples. The predictive performance of this model was then tested using the next 66 samples. Free serum teicoplanin concentrations (Cf) (mug/mL) were predicted using a simple model constructed using total serum teicoplanin (Ct) (mug/mL) and albumin concentrations (ALB) (g/dL): Cf = Ct/(1 + 1.78 * ALB). This model could estimate free serum teicoplanin concentrations with a small bias and an acceptable error. The measured free level of teicoplanin will lie between 0.63 and 1.38 times the predicted concentration in 95% of cases. Serum albumin level plays a major role in the variability of the fraction unbound of teicoplanin. This model can reliably estimate free serum teicoplanin concentrations more easily than by using direct measurements.

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

“…Consistent with the findings of studies with other patient groups (13,(19)(20)(21), the FFs of teicoplanin in the study patients were highly variable, with higher FFs being observed in patients with low serum albumin concentrations. In recent years, the importance of TDM of unbound teicoplanin concentrations has been highlighted for critically ill and chronically ill patients (13,20,21).…”

Determination of teicoplanin trough concentration target and appropriate total dose during the first 3 days: a retrospective study in patients with MRSA infections

“…We suggest that the trough concentration of teicoplanin on the fourth day to eradicate MRSA should be C13 mg/L. Age, body weight, creatinine clearance and serum albumin concentration can be factors that affect teicoplanin pharmacokinetics [22][23][24]. In this study, using multiple logistic regression analysis, we showed that the total dose per body weight had the most effect on teicoplanin clearance during the first 3 days.…”

Changes in the pharmacokinetics of teicoplanin in patients with hyperglycaemic hypoalbuminaemia: Impact of albumin glycosylation on the binding of teicoplanin to albumin

“…Unbound TEIC was separated by ultrafiltration using a YM-30 Centrifree ® device (Nihon Millipore KK, Tokyo, Japan). Certain parameters of the TDx FLx system were changed to allow a lower concentration range to be used during quantification of the serum concentration of unbound TEIC according to a modified version of the method devised by Yano et al [8]. The accuracy, linearity and precision of this method were evaluated [expressed as the percentage coefficient of variation (%CV)].…”

“…However, it has been reported that the free fraction of TEIC is increased in patients with serum albumin levels of <3.0 g/dL [8]. Moreover, patients with hypoalbuminaemia were demonstrated to have lower serum trough concentrations of TEIC than healthy volunteers [7].…”