ABSTRACT
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.
ABSTRACT
Chronic alcohol consumption is a common problem among the HIV-infected patients on HAART. The study determined the effect of chronic alcohol use on steady state plasma drug concentrations of stavudine (d4T), lamivudine (3TC) and nevirapine (NVP) in HIV-infected patients during the 9 months follow up period. It also determined whether there were some patients with undetectable plasma drug concentrations in their plasma during the follow up. A case control using repeated measures design with serial measurements model, where plasma drug concentrations were measured at 3 month intervals was used. Chronic alcohol-use using WHO AUDIT tool was used to screen patients. A total of 41 patients (21 alcohol group and 20 control group) were followed up for 9 months with blood sampling done at 3 month intervals. The Shimadzu Class-VPTM HPLC Chromatography data system version 6.1 equipment with UV detector was used to measure the plasma drug concentrations. Data was analyzed using SAS 2003 version 9.1 statistical package with repeated measures fixed the model and means were compared using the student t-test. The mean steady state plasma concentration of both d4T and 3TC in chronic alcohol use group were lower than in the control group all throughout the 9 months period of follow-up. The mean steady state plasma drug concentrations of NVP were higher in the alcohol group at 0 and 3 months and lower in the 6 and 9 months as compared to the control group. The mean total plasma NVP concentration was higher in the chronic alcohol group as compared to the control group and the difference was statistically significant (p≤0.05). However some patients had undetectable plasma drug concentrations despite of having ≥ 95 % adherence rate. Chronic alcohol use by the HIV-infected patients lowers the steady state plasma drug concentrations of d4T, 3TC and NVP in patients.