Population pharmacokinetics of teicoplanin and attainment of pharmacokinetic/pharmacodynamic targets in adult patients with haematological malignancy

Abstract

19Objectives: To describe the population pharmacokinetics of teicoplanin in adult haematological 20 malignancy patients receiving higher than standard doses and to perform Monte Carlo simulations 21 to determine dosing regimens associated with optimal teicoplanin concentrations. 22Methods: This was a hospital-based clinical trial (EudraCT 2013-004535-72). Nine blood samples 23 were collected on Day 3, plus single trough samples on Days 7 and 10, and 24 and 48 h post last 24 dose. Teicoplanin minimum inhibitory concentrations were determined for Gram-positive isolates 25 from study patients. Population pharmacokinetic analyses and Monte Carlo dosing simulations were 26 undertaken using Pmetrics®. 27Results: Thirty adult haematological malignancy patients were recruited with a mean (SD) loading 28 dose, age, total body weight and creatinine clearance of 9.5 (1.9) mg/kg, 63 (12) that administering five loading doses 12-h, stratified by total body weight and creatinine clearance, 36 increased the probability of achieving target concentrations within 72 h. 37Conclusions: To increase the number of patients achieving optimal teicoplanin concentrations an 38 individualised dosing approach, based on body weight and creatinine clearance, is recommended. 39 40

Population Pharmacokinetics and Pharmacodynamics of Teicoplanin and C‐Reactive Protein in Hospitalized Patients With Gram‐Positive Infections

“…12,[14][15][16][17]25,46,47 The final estimated value of CL (0.59 L/h) was not significantly different from the values in previous studies (CL 0.3-2.0 L/h), and the estimated value of Vd area (144 L/70 kg) was slightly larger than those of previous studies (40-110 L/70 kg). 12,[14][15][16][17]25,46,47 In the present study the volume of distribution was corrected based on the standard FFM of 56.1 kg (assumed TBW of 70 kg and height of 1.76 m). This was considered 1 of the reasons for the larger Vd area of the present study: no previous studies had evaluated the influence of FFM.…”

“…12,[14][15][16]25,46,47 The teicoplanin concentrations were mainly collected in the elimination phase, with some being from the distribution phase (Figure 1). 12,[14][15][16]25,46,47 The teicoplanin concentrations were mainly collected in the elimination phase, with some being from the distribution phase (Figure 1).…”

“…The PK model of teicoplanin was described with a 2-compartment model, whereas previous studies have used 1-, 2-, or 3-compartment models. 12,[14][15][16]25,46,47 The teicoplanin concentrations were mainly collected in the elimination phase, with some being from the distribution phase (Figure 1). Two-and 1-compartment models were evaluated, but the OFV of the 2-compartment model was significantly lower than that of the 1compartment model ( OFV 79.0, df 3, P < .05).…”

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

“…A diagnosis for each infection was based on de nitions in the guidelines issued by the National Healthcare Safety Network [13]. Infections with at least one of the following signs were analyzed: core temperature >37.8°C, total peripheral white blood cell (WBC) count >10,000/mm 3 , or C-reactive protein (CRP) >3.0 mg/dL.…”

“…For bone and joint infections and infective endocarditis, teicoplanin 12 mg/kg body weight every 12 h for three-to-ve doses is recommended [6]. In Monte Carlo simulations, a high probability of attaining the target C min of 20 μg/mL was observed using a regimen of 12 mg/kg administered at 12-h intervals for ve doses, but not when using four doses [13]. Byrne et al [14] reported the recommended loading dose to achieve a C min ≥20 μg/mL based on population PK analysis was 12 mg/kg administered every 12 h for ve doses in patients with a body weight of 70 kg and serum albumin level of 3.0 mg/dL.…”