Clinical pharmacokinetics of rifampin in patients with tuberculosis and type 2 diabetes mellitus: Association with biochemical and immunological parameters
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Tuberculosis (TB) remains a major public health issue due to the increasing incidence of type 2 diabetes mellitus (T2DM), which exacerbates the clinical course of TB and increases the risk of poor long-term outcomes. The aim of this study was to characterize the pharmacokinetics of rifampin (RIF) and its relationship with biochemical and immunological parameters in patients with TB and T2DM. The biochemical and immunological parameters were assessed on the same day that the pharmacokinetic evaluation of RIF was performed. Factors related to the metabolic syndrome that is characteristic of T2DM patients were not detected in the TB-T2DM group (where predominant malnutrition was present) or in the TB group. Percentages of CD8 T lymphocytes and NK cells were diminished in the TB and TB-T2DM patients, who had high tumor necrosis factor alpha (TNF-α) and low interleukin- 17 (IL-17) levels compared to healthy volunteers. Delayed RIF absorption was observed in the TB and TB-T2DM patients; absorption was poor and slower in the latter group due to poor glycemic control. RIF clearance was also slower in the diabetic patients, thereby prolonging the mean residence time of RIF. There was a significant association between glycemic control, increased TNF-α serum concentrations, and RIF pharmacokinetics in the TB-T2DM patients. These altered metabolic and immune conditions may be factors to be considered in anti-TB therapy management when TB and T2DM are concurrently present. Copyright © 2015, American Society for Microbiology. All Rights Reserved.
Tuberculosis (TB) remains a major public health issue due to the increasing incidence of type 2 diabetes mellitus (T2DM), which exacerbates the clinical course of TB and increases the risk of poor long-term outcomes. The aim of this study was to characterize the pharmacokinetics of rifampin (RIF) and its relationship with biochemical and immunological parameters in patients with TB and T2DM. The biochemical and immunological parameters were assessed on the same day that the pharmacokinetic evaluation of RIF was performed. Factors related to the metabolic syndrome that is characteristic of T2DM patients were not detected in the TB-T2DM group (where predominant malnutrition was present) or in the TB group. Percentages of CD8%2b T lymphocytes and NK cells were diminished in the TB and TB-T2DM patients, who had high tumor necrosis factor alpha (TNF-α) and low interleukin- 17 (IL-17) levels compared to healthy volunteers. Delayed RIF absorption was observed in the TB and TB-T2DM patients; absorption was poor and slower in the latter group due to poor glycemic control. RIF clearance was also slower in the diabetic patients, thereby prolonging the mean residence time of RIF. There was a significant association between glycemic control, increased TNF-α serum concentrations, and RIF pharmacokinetics in the TB-T2DM patients. These altered metabolic and immune conditions may be factors to be considered in anti-TB therapy management when TB and T2DM are concurrently present. Copyright © 2015, American Society for Microbiology. All Rights Reserved.
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glibenclamide plus metformin; insulin; interleukin 10; interleukin 17; isoniazid plus pyrazinamide plus rifampicin; rifampicin; tumor necrosis factor alpha; interleukin 17; rifampicin; tuberculostatic agent; tumor necrosis factor; adult; aged; antibiotic therapy; area under the curve; Article; biochemical composition; CD8 T lymphocyte; controlled study; diabetic patient; drug absorption; drug blood level; drug clearance; drug half life; evaluation study; female; glycemic control; human; human cell; immunological parameters; insulin treatment; longitudinal study; major clinical study; male; malnutrition; maximum plasma concentration; mean residence time; metabolic syndrome X; natural killer cell; non insulin dependent diabetes mellitus; priority journal; prospective study; protein blood level; short course therapy; single drug dose; time to maximum plasma concentration; tuberculosis; adolescent; CD4 T lymphocyte; complication; drug effects; half life time; immunology; lung tuberculosis; metabolism; middle aged; non insulin dependent diabetes mellitus; young adult; Adolescent; Adult; Aged; Antitubercular Agents; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Diabetes Mellitus, Type 2; Female; Half-Life; Humans; Interleukin-17; Killer Cells, Natural; Male; Middle Aged; Rifampin; Tuberculosis, Pulmonary; Tumor Necrosis Factor-alpha; Young Adult
glibenclamide plus metformin; insulin; interleukin 10; interleukin 17; isoniazid plus pyrazinamide plus rifampicin; rifampicin; tumor necrosis factor alpha; interleukin 17; rifampicin; tuberculostatic agent; tumor necrosis factor; adult; aged; antibiotic therapy; area under the curve; Article; biochemical composition; CD8+ T lymphocyte; controlled study; diabetic patient; drug absorption; drug blood level; drug clearance; drug half life; evaluation study; female; glycemic control; human; human cell; immunological parameters; insulin treatment; longitudinal study; major clinical study; male; malnutrition; maximum plasma concentration; mean residence time; metabolic syndrome X; natural killer cell; non insulin dependent diabetes mellitus; priority journal; prospective study; protein blood level; short course therapy; single drug dose; time to maximum plasma concentration; tuberculosis; adolescent; CD4+ T lymphocyte; complication; drug effects; half life time; immunology; lung tuberculosis; metabolism; middle aged; non insulin dependent diabetes mellitus; young adult; Adolescent; Adult; Aged; Antitubercular Agents; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Diabetes Mellitus, Type 2; Female; Half-Life; Humans; Interleukin-17; Killer Cells, Natural; Male; Middle Aged; Rifampin; Tuberculosis, Pulmonary; Tumor Necrosis Factor-alpha; Young Adult
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