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A Two-Dose Oritavancin Regimen Using Pharmacokinetic Estimation Analysis

Warren E Rose1, Paul R Hutson2

  • 1School of Pharmacy, University of Wisconsin-Madison, Madison, WI, 53705, USA. warren.rose@wisc.edu.

Drugs - Real World Outcomes
|June 27, 2020
PubMed
Abstract

Insights

A two-dose oritavancin regimen (1200 mg followed by 800 mg one week later) maintains therapeutic concentrations for longer than a single dose, offering a potential option for prolonged treatment of multidrug-resistant Gram-positive infections.

Area of Science:

  • Pharmacokinetics and Pharmacodynamics
  • Infectious Diseases
  • Antimicrobial Therapy

Background:

  • Limited treatment options exist for complicated, multidrug-resistant Gram-positive infections requiring prolonged therapy.
  • Oritavancin is approved as a single 1200 mg dose for skin infections, but supplemental doses have been reported.

Purpose of the Study:

  • To determine population pharmacokinetic estimates for a 1200 mg single oritavancin dose compared to a two-dose regimen (1200 mg followed by 800 mg one week later).

Main Methods:

  • Simulated administration of a 1200 mg oritavancin dose over 3 hours, followed 7 days later by a simulated 800 mg dose over 3 hours.
  • Population pharmacokinetic estimation was performed.

Main Results:

  • The two-dose oritavancin regimen demonstrated predictable linear pharmacokinetics and achieved therapeutic concentrations.
  • Total and free oritavancin concentrations remained above the susceptibility breakpoint for 8 weeks and 4.6 weeks, respectively, significantly longer than the single-dose regimen.
  • The two-dose regimen resulted in a greater area under the drug concentration-time curve (AUC) above the susceptibility breakpoint and maintained a high AUC:MIC ratio for specific MIC values.

Conclusions:

  • The 1200 mg followed by 800 mg regimen provides extended therapeutic concentrations.
  • This dosing strategy warrants further investigation for prolonged oritavancin treatment in indicated cases, supported by existing observational data.

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