Population Pharmacokinetics of Telavancin in Healthy Subjects and Patients with Infections

Abstract

A population pharmacokinetic model of telavancin, a lipoglycopeptide antibiotic, was developed and used to identify sources of interindividual variability. Data were obtained from healthy subjects (seven phase 1 studies), patients with complicated skin and skin structure infections (cSSSI; two phase 2 and two phase 3 studies), and patients with hospital-acquired pneumonia (HAP; two phase 3 studies). A two-compartment open model with zero-order input best fit the telavancin data from healthy individuals and patients with cSSSI or HAP. Telavancin clearance was highly correlated with renal function and, to a lesser extent, with body weight. Other covariates were related to at least one parameter in cSSSI (gender, bacterial eradication, and surgery) or HAP (age of >75 years) but did not markedly affect exposure. These analyses support current dosing recommendations for telavancin based on patient weight and renal function.

Telavancin (VIBATIV) for the treatment of complicated skin and skin structure infections

“…The clearance of telavancin in patients with cSSSIs was 0.93 l/h similar to what was demonstrated in healthy subjects [36]. In patients with cSSSI, telavancin clearance was shown to be slightly higher in males but this difference is thought to be minimal and of slight clinical relevance.…”

In Vitro Pharmacodynamics of Human Simulated Exposures of Telavancin against Methicillin-Susceptible and -Resistant Staphylococcus aureus with and without Prior Vancomycin Exposure

“…Humanized free drug exposures of vancomycin at 1 g every 12 h (q12h) were simulated based on the mean parameter estimates from a population pharmacokinetic model where the target area under the free drug concentration-time curve from 0 to 12 h (fAUC 0 -12 ) for vancomycin was 105 g · h/ml based on targeting a free peak concentration of 14 g/ml, a free trough concentration of 5 g/ml, and a half-life of 8.2 h (16). Likewise, telavancin exposure was simulated at a dose of 750 mg (10 mg/kg, assuming a 75-kg patient) q24h based on the mean parameter estimates from the population pharmacokinetic model published by Samara and colleagues (17) where the target fAUC 0 -24 was 80.1 g · h/ml and was obtained through targeting a free peak of 10.7 g/ml, a free trough of 1.25 g/ml, and a half-life of 1.1 h for the first hour (to simulate the distribution phase) and 9.9 h from 1 to 24 h (to simulate the terminal elimination phase). The protein binding rates of vancomycin and telavancin were assumed to be 50% and 90%, respectively, when free drug exposures were simulated (17,18).…”

“…Likewise, telavancin exposure was simulated at a dose of 750 mg (10 mg/kg, assuming a 75-kg patient) q24h based on the mean parameter estimates from the population pharmacokinetic model published by Samara and colleagues (17) where the target fAUC 0 -24 was 80.1 g · h/ml and was obtained through targeting a free peak of 10.7 g/ml, a free trough of 1.25 g/ml, and a half-life of 1.1 h for the first hour (to simulate the distribution phase) and 9.9 h from 1 to 24 h (to simulate the terminal elimination phase). The protein binding rates of vancomycin and telavancin were assumed to be 50% and 90%, respectively, when free drug exposures were simulated (17,18). All simulations were performed on ADAPT 5 (USC Biomedical Simulations Resource, Los Angeles, CA).…”

Telavancin in the treatment of Staphylococcus aureus hospital-acquired and ventilator-associated pneumonia: clinical evidence and experience

“…Consequently, it is advised that patients treated with TLV should have their renal function (serum Cr and urinary output) monitored daily for at least the first 3-5 days of therapy and every 48-72 h thereafter. If renal function is found to markedly decrease, then the continuation of therapy should be assessed [Samara et al 2012].…”