Volume 17 Supplement 3

Seventh International Symposium on Intensive Care and Emergency Medicine for Latin America

Open Access

A phase 1 study of intravenously administered TR-701 FA in subjects with advanced renal impairment

  • S Flanagan1,
  • D Morris2,
  • T Boyea1,
  • H Dreskin1,
  • SL Minassian1,
  • H Alcorn3,
  • T Marbury4,
  • M Abdelhameed2,
  • E Fang1 and
  • P Prokocimer1
Critical Care201317(Suppl 3):P25

https://doi.org/10.1186/cc12641

Published: 19 June 2013

Introduction

The objective of the study was to characterize the safety of tedizolid phosphate (TR-701 FA) and the pharmacokinetics of tedizolid (TR-700), its microbiologically active moiety, in subjects with advanced renal impairment (eGFR <30 ml/minute/1.73 m2, not on dialysis) compared with matched subjects with normal renal function (eGFR ≥80.0 ml/minute/1.73 m2).

Methods

Eight subjects with advanced renal impairment and eight matched controls (by age, gender, and body mass index) received a single intravenous infusion of 200 mg TR-701 FA. Serial plasma PK samples were collected from pre-dose through 72 hours post-dose. Plasma samples were analyzed for TR-700 and the following pharmacokinetic parameters were calculated: Cmax, tmax, AUC0−∞, AUC0−t λz, CLsys, and plasma t 1 / 2 .

Results

Baseline eGFR ranged from 7 to 28 ml/minute/1.73 m2 (including three subjects with eGFR <15 ml/minute/1.73 m2). The pharmacokinetics of TR-700 was essentially unchanged in subjects with advanced renal impairment relative to a matched control group. Approximately 8% lower AUC and nearly identical Cmax values were observed in renal impaired subjects relative to matched controls, and other pharmacokinetic parameters were also similar between groups. See Table 1.
Table 1

Pharmacokinetic parameters of tedizolid in control and renal impaired subjects

 

Geometric mean (GM)

90% Cl

TR-700

Advanced renal impairment

Control

GM ratio

Lower

Upper

AUC0-t (μg·hour/ml)

28.4

30.7

0.93

0.70

1.23

AUC0-∞ (μg·hour/ml)

28.7

31.0

0.92

0.70

1.23

Cmax (μg/ml)

3.01

3.02

0.99

0.78

1.27

Conclusion

The TR-700 plasma pharmacokinetic results from this study provide support that no dose adjustment is needed in subjects with advanced renal impairment.

Declarations

Acknowledgements

Trial registration: NCT01452828.

Authors’ Affiliations

(1)
Trius Therapeutics
(2)
CovanceMadison
(3)
DaVita, Minneapolis
(4)
Orlando Clinical Research Center

Copyright

© Flanagan et al; licensee BioMed Central Ltd. 2013

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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