Faculty Collaboration Database

Pharmacokinetics of Telavancin at Fixed Doses in Normal-Body-Weight and Obese (Classes I, II, and III) Adult Subjects. Antimicrob Agents Chemother 2018 Apr;62(4)

Date

01/10/2018

Pubmed ID

29311094

Pubmed Central ID

PMC5913990

DOI

10.1128/AAC.02475-17

Scopus ID

2-s2.0-85044519836 (requires institutional sign-in at Scopus site)   15 Citations

Abstract

A recommended total-body-weight (TBW) dosing strategy for telavancin may not be optimal in obese patients. The primary objective of this study was to characterize and compare the pharmacokinetics (PK) of telavancin across four body size groups: normal to overweight and obese classes I, II, and III. Healthy adult subjects (n = 32) received a single, weight-stratified, fixed dose of 500 mg (n = 4), 750 mg (n = 8), or 1,000 mg (n = 20) of telavancin. Noncompartmental PK analyses revealed that subjects with a body mass index (BMI) of ≥40 kg/m² had a higher volume of distribution (16.24 ± 2.7 liters) than subjects with a BMI of <30 kg/m² (11.71 ± 2.6 liters). The observed area under the concentration-time curve from time zero to infinity (AUC_0-∞) ranged from 338.1 to 867.3 mg · h/liter, with the lowest exposures being in subjects who received 500 mg. AUC_0-∞ values were similar among obese subjects who received 1,000 mg. A two-compartment population PK model best described the plasma concentration-time profile of telavancin when adjusted body weight (ABW) was included as a predictive covariate. Fixed doses of 750 mg and 1,000 mg had similar target attainment probabilities for efficacy as doses of 10 mg/kg of body weight based on ABW and TBW, respectively. However, the probability of achieving a target area under the concentration-time curve from time zero to 24 h of ≥763 mg · h/liter in association with acute kidney injury was highest (19.7%) with TBW-simulated dosing and lowest (0.4%) at the 750-mg dose. These results suggest that a fixed dose of 750 mg is a safe and effective alternative to telavancin doses based on TBW or ABW for the treatment of obese patients with normal renal function and Staphylococcus aureus infections. (This study has been registered at ClinicalTrials.gov under identifier NCT02753855.).

Author List

Bunnell KL, Pai MP, Sikka M, Bleasdale SC, Wenzler E, Danziger LH, Rodvold KA

Author

Kristen B. Bresnehan PharmD Associate Professor in the School of Pharmacy Operations department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Aminoglycosides
Anti-Bacterial Agents
Body Weight
Humans
Ideal Body Weight
Models, Theoretical
Obesity
Staphylococcal Infections