Meta-Analysis of Clinical Studies Supports the Pharmacokinetic Variability Hypothesis for Acquired Drug Resistance and Failure of Antituberculosis Therapy | Zendy

Jotam G. Pasipanodya | Zendy; Shashikant Srivastava | Zendy; Tawanda Gumbo | Zendy

Open Access

Meta-Analysis of Clinical Studies Supports the Pharmacokinetic Variability Hypothesis for Acquired Drug Resistance and Failure of Antituberculosis Therapy

Author(s) -

Jotam G. Pasipanodya,

Shashikant Srivastava,

Tawanda Gumbo

Publication year - 2012

Publication title -

clinical infectious diseases

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 3.44

H-Index - 336

eISSN - 1537-6591

pISSN - 1058-4838

DOI - 10.1093/cid/cis353

Subject(s) - medicine , isoniazid , confidence interval , pharmacokinetics , sputum , relative risk , dosing , regimen , randomized controlled trial , drug resistance , clinical trial , meta analysis , tuberculosis , drug , pharmacology , intensive care medicine , pathology , microbiology and biotechnology , biology

Using hollow-fiber tuberculosis studies, we recently demonstrated that nonadherence is not a significant factor for ADR and that therapy failure only occurs after a large proportion of doses are missed. Computer-aided clinical trial simulations have suggested that isoniazid and rifampin pharmacokinetic variability best explained poor outcomes. We were interested in determining whether isoniazid pharmacokinetic variability was associated with either microbiological failure or ADR in the clinic.

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