A Two-Dose Oritavancin Regimen Using Pharmacokinetic Estimation Analysis

Abstract

Background: Antibiotics for the treatment of complicated, multidrug-resistant Gram-positive infections are limited, especially when prolonged treatment is necessary. Oritavancin is approved for the treatment of serious skin infections as a 1200 mg single-dose regimen, but case reports describe supplemental doses given at weekly intervals ranging from 800 mg to 1200 mg. Objective: This study determined population pharmacokinetic estimates for a 1200 mg single dose with and without an 800 mg dose 1 week apart. Methods: A simulated oritavancin 1200 mg dose was infused over 3 h followed 7 days later by a simulated 800 mg dose infused over 3 h for pharmacokinetic estimation. Results: The oritavancin dosing displayed predictable linear pharmacokinetics and therapeutic concentrations. The total and free oritavancin concentrations remained above the susceptibility breakpoint (0.12 mg/L) for 8 weeks and 4.6 weeks, respectively, with the two-dose regimen. This was significantly greater than the single-dose regimen. This regimen also results in a greater area under the drug concentration–time curve (AUC) above the susceptibility breakpoint compared to the single-dose regimen (p < 0.001), and it maintains a high AUC:minimum inhibitory concentration (MIC) ratio against organisms with MICs up to 0.25 mg/L. Conclusion: These results along with the observational clinical reports of success and safety with this dosing scheme of 1200 mg followed by 800 mg 7 days later provide evidence for further evaluation of this approach when prolonged oritavancin treatment may be indicated.