The value of in vitro drug activity and pharmacokinetics in predicting the effectiveness of antimycobacterial therapy: a critical review

The American Journal of the Medical Sciences
W J Burman

Abstract

Marked increases in case rates of drug-resistant tuberculosis and nontuberculous mycobacterial infections have brought renewed urgency to the development of new treatment regimens for mycobacterial infections. Preclinical data, such as in vitro measures of drug activity and pharmacokinetics, are used in the design of new treatment regimens. This review surveys the extensive published clinical experience concerning the treatment of drug-susceptible tuberculosis to evaluate the use of these preclinical measures in predicting clinical outcomes of antimycobacterial therapy. In vitro measures of drug activity predict the potency of a drug to prevent the emergence of resistance to other antimycobacterial drugs but do not predict the sterilizing activity of a drug or the activity of drug combinations. In vitro measures of drug activity do not allow reliable predictions of the level at which an organism should be considered resistant. Assays of drug penetration in tissues and activity against intracellular bacilli add modestly to the predictive value of in vitro measures of drug activity but still do not predict sterilizing activity. In contrast, animal models of tuberculosis have predicted relative drug potency (including sterilizing ...Continue Reading

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Citations

Aug 17, 2002·Bioorganic & Medicinal Chemistry Letters·Daniela UbialiMarco Terreni
Mar 26, 2010·The Journal of Antimicrobial Chemotherapy·Alberto CoronaMervyn Singer
Jan 11, 2007·Antimicrobial Agents and Chemotherapy·Sang Hyun ChoScott G Franzblau
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Jan 9, 2004·Infectious Disease Clinics of North America·Stéphane CarrynPaul M Tulkens

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