Clinical Pharmacokinetics of Rifampin in Patients with Tuberculosis and Type 2 Diabetes Mellitus: Association with Biochemical and Immunological Parameters

Abstract

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-␣) 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-␣ 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.

Effect of Diabetes Mellitus on the Pharmacokinetics and Pharmacodynamics of Tuberculosis Treatment

“…A subsequent study by the same group, however, showed that these differences disappeared when weight was a matching factor (22). Data from other settings are mixed, with some studies showing a reduced and slower absorption of rifampin (with a lower C max ) with DM (18,19) and others showing no meaningful effect of DM on rifampin PK (21). It is likely that discrepancies in the results can be attributed to differences in demographics, DM severity, drug dosing, and study design.…”

“…A few studies have evaluated the effect of DM on the pharmacokinetics (PK) of antituberculosis drugs, and the results have been mixed, with some reporting lower anti-TB drug concentrations in people with DM (17)(18)(19)(20) and others showing no effect of DM on first-line drug exposures (21)(22)(23). In the context of a large prospective cohort study involving patients with and without DM in India, we evaluated the effects of DM (and the HbA1c value) on first-line anti-TB drug pharmacokinetics.…”

Fixed-dose combination associated with faster time to smear conversion compared to separate tablets of anti-tuberculosis drugs in patients with poorly controlled diabetes and pulmonary tuberculosis in Qatar

“…On the other hand, a pharmacokinetic study was conducted on TB patients with and without DM who received 3FDC showed that there was no difference between the groups in RIF maximum concentration achieved and area under the curve. However, diabetic patients needed longer time to achieve RIF maximum concentration [ 15 ].…”

A Pilot Study of Immune Activation and Rifampin Absorption in HIV-Infected Patients without Tuberculosis Infection: A Short Report

“…The impact of HIV disease on the patient's capacity to absorb specific drugs and nutrients merits further investigation, with a particular need to understand variability in rifampin absorption in relation to immunologic parameters [ 17 ]. We sought to describe the relationship between HIV-associated immune activation, measures of intestinal absorptive capacity and permeability, and rifampin absorption among HIV-infected individuals naïve to antiretroviral therapy.…”