Dalbavancin dosage adjustments not required for patients with mild to moderate renal impairment

Introduction

Dalbavancin (DAL) is a novel semisynthetic glycopeptide in phase 3 clinical development that has activity against Gram(+) organisms, including resistant strains. Two doses given 1 week apart have been shown to be effective in complicated skin and soft tissue infections. A clinical study was performed to determine the need for dosage adjustments in subjects with mild to moderate renal impairment (RI).

Methods

Subjects with normal renal function (creatinine clearance (CrCL) > 80 ml/min), mild RI (CrCL of 50–79 ml/min), or moderate RI (CrCL of 30–49 ml/min) received DAL as a single intravenous infusion (1,000 mg). Plasma samples were collected through at least 14 days after the dose. DAL was assayed using validated LC-MS/MS methods. Pharmacokinetic (PK) data were analyzed using noncompartmental methods.

Results

Twenty-one subjects were enrolled, received one dose of 1,000 mg dalbavancin, and were included in the PK analysis. Plasma concentration–time curves through 14 days (AUC0-14) were similar between subjects with normal renal function and subjects with mild or moderate RI. An increased concentration was observed in subjects with moderate RI beyond day 14, at a point in the profile when concentrations were below 40 m/l (Figure 1).

Figure 1

Conclusion

DAL does not require a dosage adjustment for patients with mild or moderate RI. These results are consistent with previous clinical and nonclinical PK studies showing that DAL has dual (both renal and nonrenal) routes of elimination.