Utility of Rifampin Blood Levels in the Treatment and Follow-up of Active Pulmonary Tuberculosis in Patients who Were Slow to Respond to Routine Directly Observed Therapy

Drug Induced Hepatotoxicity of Antituberculosis Drugs and Their Serum Levels

“…However, recent antimicrobial pharmacokinetic-pharmacodynamic studies have suggested that PZA doses that are higher than the currently recommended doses may be more efficacious (24). There are also reports that suggest that a higher dose of RMP is efficacious without serious adverse effects (25)(26)(27). A number of previous studies showed that low serum levels of INH and/or RMP could be problematic because they are associated with low therapeutic efficacy and relatively high therapeutic failure (28)(29)(30).…”

Simultaneous Determination of Isoniazid, Pyrazinamide, Rifampicin and Acetylisoniazid in Human Plasma by High-Performance Liquid Chromatography

“…However, some patients experience treatment failure because of a low blood drug concentration. 3,4 Acetylisoniazid (AcINH), the major metabolite of INH, is metabolized by N-acetyltransferase type 2 in the liver, including slow and fast acetylator phenotypes. 5 The side effects and therapeutic effectiveness of INH are different from that of the acetylator phenotype.…”

“…6 After adjusting the dose treatment according to blood drug concentration monitoring, most patients of treatment failure were successfully treated. 3,7 Therefore, plasma drug concentration monitoring is very important to improve the effectiveness of the therapy of TB patients.…”

An interlaboratory quality control programme for the measurement of tuberculosis drugs

“…Inadequate exposure to TB drugs constitutes one of the main factors underlying suboptimal treatment response and development of resistance, as evidenced by results from: the in vitro hollow fibre model [1]; clinical studies on relationships between drug concentrations and response [2-5]; a pharmacogenetic trial [6]; and a recent meta-analysis [7].More specifically, these concentration-effect evaluations suggest that clinicians should prescribe higher doses of rifampicin [2,5], that acetylator status should be used to determine the dose of isoniazid [6,7], and that higher doses and exposures to pyrazinamide may increase efficacy [4,5].Clearly, such studies also underline the relevance of careful concentration-effect evaluations during the development of new TB drugs that will eventually be applied by clinicians all over the world.Finally, these studies support the concept of therapeutic drug monitoring (TDM) of TB drugs as applied by clinicians and pharmacists in selected centres around the world [8][9][10]. In contrast to administering the same fixed dose to all patients, TDM seeks to individualise drug doses, guided by measurement of serum (or plasma) drug concentrations.…”

“…More specifically, these concentration-effect evaluations suggest that clinicians should prescribe higher doses of rifampicin [2,5], that acetylator status should be used to determine the dose of isoniazid [6,7], and that higher doses and exposures to pyrazinamide may increase efficacy [4,5].…”