Intrapatient variability in plasma rifampicin & isoniazid in tuberculosis patients

Background & objectives: Large variability in anti-tuberculosis (TB) drug concentrations between patients is known to exist. However, limited information is available on intrapatient drug levels during the course of anti-TB treatment (ATT). This study was conducted to evaluate intrapatient variability in plasma rifampicin (RMP) and isoniazid (INH) concentrations during ATT at start of the treatment, at the end of intensive phase (IP) of ATT and at the end of ATT in adult TB patients being treated in the Revised National TB Control Programme (RNTCP). Methods: Adult TB patients (n=485), receiving thrice-weekly ATT in the RNTCP, were studied. Two-hour post-dosing concentrations of RMP and INH were determined at month 1, end of IP and end of ATT, after directly observed drug administration. Drug concentrations were estimated by high-performance liquid chromatography. Results: The median (inter-quartile range) RMP concentrations during the first month, at end of IP and end of ATT were 2.1 (0.4-5.0), 2.4 (0.6-5.5) and 2.2 (0.5-5.3) ?g/ml, respectively. The corresponding INH concentrations were 7.1 (4.2-9.9), 7.2 (3.9-10.9) and 6.7 (3.9-9.5) ?g/ml. None of the differences in drug concentrations obtained at different time points during ATT were significant. RMP and INH concentrations at different time points were significantly correlated. Age and body mass index caused significant variability in drug concentrations. Interpretation & conclusions: Plasma RMP and INH estimations in adult TB patients at two hours after drug administration remained unaltered during ATT. Clinicians can consider testing drug concentrations at any time point during ATT. These findings may assume significance in the context of therapeutic drug monitoring of anti-TB drug concentrations.

Biosynthesis and characterization of keratinolytic protease from actinobacterium sp. in solid state culture.

The aim of this study was to use agro-industrial residues for the production of a halotolerant keratinolytic- protease by Actinobacterium sp. in solid-state fermentation. Among various agro-industrial residues that were evaluated, apple pomace supported maximum protease production (8400 U/g material). The optimum conditions required for enzyme production were a fermentation period of 72 h, 10% (w/v) NaCl, pH 7.0, 120% (v/w) moisture and 10% (v/w) inoculum. The enzyme exhibited activity to a range of pH (7.0-9.0) and temperature (30-45°C), with optima at 8.0 and 40 °C, respectively. Most of the divalent ions tested stimulated the protease activity and Ca2+ ion was required for its activity and stability. The enzyme was widely active at the range of NaCl concentration (5%-15%, w/v) and effectively degraded chicken feather. This protease could be useful in fish sauce fermentation and also in feed industry.