Altered pharmacokinetics of antituberculosis drugs may contribute to an increased risk of tuberculosis treatment failure for diabetic patients. We previously found that rifampin exposure was 2-fold lower in diabetic than in nondiabetic tuberculosis patients during the continuation phase of treatment. We now examined the influence of diabetes on the pharmacokinetics of antituberculosis drugs in the intensive phase of tuberculosis treatment, and we evaluated the effect of glycemic control. For this purpose, 18 diabetic and 18 gender-and body weight-matched nondiabetic tuberculosis patients were included in an Indonesian setting. Intensive pharmacokinetic sampling was performed for rifampin, pyrazinamide, and ethambutol at steady state. The bioavailability of rifampin was determined by comparing rifampin exposure after oral versus intravenous administration. Pharmacokinetic assessments were repeated for 10 diabetic tuberculosis patients after glycemic control. No differences in the areas under the concentrationtime curves of the drugs in plasma from 0 to 24 h postdose (AUC 0-24 ), the maximum concentrations of the drugs in plasma (C max ), the times to C max (T max ), and the half-lives of rifampin, pyrazinamide, and ethambutol were found between diabetic and nondiabetic tuberculosis patients in the intensive phase of tuberculosis treatment. For rifampin, oral bioavailability and metabolism were similar in diabetic and nondiabetic patients. The pharmacokinetic parameters of antituberculosis drugs were not correlated with blood glucose levels or glucose control. We conclude that diabetes does not alter the pharmacokinetics of antituberculosis drugs during the intensive phase of tuberculosis treatment. The reduced exposure to rifampin of diabetic patients in the continuation phase may be due to increased body weight and possible differences in hepatic induction. Further research is needed to determine the cause of increased tuberculosis treatment failure among diabetic patients.Diabetes mellitus (DM) is a well-known risk factor for tuberculosis (TB) (1, 3, 7), with prevalence rates among TB patients ranging from 10 to 30% (1,24,25). There is a rapid increase in the global prevalence of DM, especially in developing countries, where TB is highly endemic. It is estimated that by the year 2030, 80% of DM patients will live in the high-burden countries for TB (28). As a result, the number of TB patients with DM will increase further (19).Diabetes exerts a negative effect on TB treatment, especially among patients with poor glycemic control, with more treatment failure and more relapse than among TB patients in general (2,3,7,24). One of the possible underlying mechanisms could be altered pharmacokinetics of anti-TB drugs. Lower concentrations of anti-TB drugs in plasma have been associated with clinical failure and acquired drug resistance (11, 23). Our previous study showed that the mean exposure to rifampin (expressed as the area under the concentration-time curve of the drug in plasma from 0 to 6 h postdose [AUC 0-6 ])...
