Dosing and development of antimicrobial and antiviral drugs determined by restriction of resistant mutant selection

US6406881B2 · kind B2 · utility

Assignee

• The Public Health Research Institute Of the City of New York, Inc. · US

Inventors

• Yuzhi Dong · Great Neck, US
• Karl Drlica · New York, US
• Xilin Zhao · Penfield, US

Key dates

• Filing date: Jul 9, 2001
• Grant date: Jun 18, 2002
• Expiry date: Jul 9, 2021

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C12Q1/18
• WIPO field: Biotechnology
• WIPO sector: Chemistry

Abstract

The invention is based on the discovery that, for many drugs (e.g., antiviral or antimicrobial drugs such as antifungal or antibacterial drugs, including bacteriocidal or bacteriostatic drugs) and many pathogen strains (e.g., viral, fungal, or bacterial pathogens), a concentration of drug can be identified at which drug-resistant mutant pathogen strains are not selected. This concentration is herein referred to as the “mutant prevention concentration” (MPC). Maintaining serum concentrations of the drug above the MPC throughout a course of treatment should severely restrict selection of drug-resistant mutants. Additionally, it is discovered that drug-resistant mutant pathogens are selected exclusively within a drug concentration window, termed the “mutant selection window” (MSW). A quantitative expression of this window, which we call the “window index” (WI), is defined as the ratio of the MPC to the MIC. The window index is characteristic of a given drug and a given pathogen.