Plasma Concentrations of Isoniazid and Rifampin Are Decreased in Adult Pulmonary Tuberculosis Patients with Diabetes Mellitus

Abstract

Plasma isoniazid and rifampin concentrations, but not pyrazinamide and ethambutol concentrations, were decreased by about 50% (P < 0.05) in diabetic pulmonary tuberculosis patients. The prevalences of subnormal plasma isoniazid, rifampin, pyrazinamide, and ethambutol concentrations were 49% or 100% (P < 0.01), 66% or 100% (P < 0.05), 30% or 50% (P ‫؍‬ 0.198), and 32% or 21% (P ‫؍‬ 0.742) in nondiabetic or diabetic tuberculosis patients, respectively. These data show that plasma concentrations of isoniazid and rifampin were greatly reduced in diabetic tuberculosis patients. Diabetes mellitus (DM) is among the well-known major risk factors for tuberculosis (TB) (1-5), and the presence of DM affects the outcome of drug treatment negatively, reduces the cure rate, and enhances the risk of relapse and emergence of drug resistance (6-10). A recent study (11) has shown that DM is associated with slow response, and circulating levels of TB drugs (e.g., rifampin) are likely to be below the expected therapeutic ranges among diabetic TB patients. The circulating concentration of rifampin was also reported to decline in some (12) but not all (13, 14) studies in diabetic TB patients. Available data, however, are inconclusive with regard to whether DM affects serum therapeutic levels of anti-TB drugs.Hence, the present study was designed to determine plasma concentrations of isoniazid, rifampin, pyrazinamide, and ethambutol, the first line anti-TB drugs, in adult Turkish pulmonary tuberculosis patients with DM during the intensive phase of the short-course therapy under conditions of directly observed therapy (DOT).A total of 70 adult patients with newly diagnosed active pulmonary TB were enrolled in the study. Patients were divided into two groups. The first group consisted of 14 TB patients with type 2 DM who were receiving DM therapy with good glucose control (glycosylated hemoglobin level Ͻ 6.5%) at the time of recruitment, and they continued to use their antidiabetes drugs during the study. The second group consisted of 56 nondiabetic TB patients who were screened for DM, and patients with suspicious test results (fasting blood glucose Ͼ 100 mg/dl and/or hemoglobin A1c [HbA1c] Ͼ 6%) were excluded. Diagnosis of pulmonary TB was based on clinical symptoms, chest radiological examination, sputum microscopy, and culture. Patients with a comorbid disease (except for DM) as well as those using concomitant medications (except for antidiabetics) and having abnormal renal and/or hepatic function were excluded.Written informed consent was obtained from all patients before the commencement of the study. The study protocol and the contents of the written consent form were approved by the Institutional Ethics Committee (Acibadem University Ethical Committee, Istanbul, Turkey).All patients were administered orally identical drugs from a national manufacturer (Koçak Farma, Istanbul, Turkey) under conditions of DOT. Patients received daily administration of 300 mg of isoniazid, 600 mg of rifampin, 1,500 mg of pyrazinamide, and 1,000 mg ...

Factors Influencing Tuberculosis Treatment Outcome in Adult Patients Treated with Thrice-Weekly Regimens in India

“…Babalik et al reported that the plasma INH concentration at 2 h postdosing was lower in patients with TB and DM than those with TB (17). These decreases are most likely due to higher body weights of TB patients with DM and, hence, the lower drug doses (in milligrams per kilogram of body weight) received by TB patients with DM than those without DM.…”

The effect size of type 2 diabetes mellitus on tuberculosis drug resistance and adverse treatment outcomes

“…However, overweight and obesity is not routinely taken into account for drug adjustment during TB treatment. Thus, it is possible that TB-2DM patients who are overweight are receiving suboptimal doses of TB medications, and could be contributing to their reported lower plasma levels (Babalik et al, 2013;Nijland et al, 2006;Ruslami et al, 2007). In these studies, suboptimal levels of TB medications have been attributed to chronic hyperglycemia or to a possible interaction between drugs for the management of DM and TB (Baker et al, 2011;Ruslami et al, 2010).…”

“…Possible explanations for these pharmacokinetic alterations are related with the interactions between drugs for TB and T2DM, reduced absorption or defective liver function in T2DM patients. (Babalik et al, 2013;Baker et al, 2011;Nijland et al, 2006;Ruslami et al, 2010;Ruslami et al, 2007).…”

Optimizing treatment outcome of first-line anti-tuberculosis drugs: the role of therapeutic drug monitoring

“…Several studies have investigated the effect of DM on the plasma concentrations of first-line anti-TB drugs [61,[66][67][68][69][70]. The results, however, are conflicting; in some studies, DM was associated with decreased plasma levels of rifampicin and isoniazid [66,69,70], whereas in others, there was no clear relationship between the plasma concentrations of first-line anti-TB drugs and DM [61,67,68]. It should be noted that in some studies, only the 2-and 6-h plasma concentrations of the anti-TB drugs were measured, whereas for other studies, the intensive blood sampling or the population pharmacokinetic approach was used.…”