Impact of diabetes mellitus on rifampicin's plasma concentration and bioavailability in patients with tuberculosis: A systematic review and meta-analysis study.

AIM OF STUDY: To assess the impact of diabetes mellitus on plasma concentration and bioavailability of rifampicin. METHODS: Web of Science, Cochrane Library, PubMed and Scopus databases were screened until September 2020 on studies reported rifampicin's plasma concentration, bioavailability among diabetic tuberculosis patients and non-diabetic tuberculosis patients. According to the presence or absence of heterogeneity, the pooled estimate was operated by a random or fixed effect model. Sensitivity analysis or subgroup analysis were conducted. Attributed risk fraction of diabetes mellitus in the incidence of low rifampicin's plasma concentration 2-h after administration was calculated. RESULTS: Seventeen studies including 3478 tuberculosis patients were included in this study. Diabetic tuberculosis patients had 1.59 folds incidence of low rifampicin's plasma concentration 2-h after administrations (risk ratio 1.59, 95% confidence interval (1.16, 2.19), p = 0.004) and lower rifampicin's plasma concentration 2-h after administrations (mean difference -1.4, 95% confidence interval (-2.65,-0.15), p = 0.03) compared with non-diabetic tuberculosis patients. The attributed risk fraction of diabetes mellitus in the incidence of low rifampicin's plasma concentration 2-h after administration was 37%. There were no significant difference in rifampicin's maximum plasma concentration, event of low maximum plasma concentration, bioavailability and half-life between both groups. CONCLUSION: Diabetes mellitus attributed with 37% of low rifampicin's plasma concentration 2-h after administration but not influenced rifampicin's maximum plasma concentration, bioavailability and half-life. The negative effect of diabetes on plasma concentration 2hours after administration was influenced by diabetes management, income level, type of tuberculosis and its recurrence.

The impact of diabetes mellitus on the pharmacokinetics of rifampicin among tuberculosis patients: A systematic review and meta-analysis study.

BACKGROUND AND AIMS: Diabetes mellitus has a negative impact on the treatment outcome of tuberculosis, increasing the incidence of treatment failure and relapse. There is a scarcity of knowledge concerning the impact of diabetes mellitus on the pharmacokinetics of rifampicin. This study was conducted to evaluate the impact of diabetes mellitus on the pharmacokinetics of rifampicin among patients with tuberculosis. METHODS: We explored the Web of Science, Cochrane Library, PubMed, and Scopus databases for articles that reported the pharmacokinetic parameters of rifampicin in diabetic and nondiabetic patients with tuberculosis published until September 2020. Based on the presence or absence of heterogeneity, pooled estimates were calculated using a random or fixed effect model. RESULTS: Seven studies were relevant and included in this study. The Tmax of rifampicin increased in diabetic patients with tuberculosis compared with nondiabetic patients with tuberculosis (MD 0.84, 95% CI (0.32, 1.35), p = 0.002). No significant differences were detected in rifampicin Cmax (MD 0.18, 95% CI (-0.52, 0.88), p = 0.61), AUC0-24 (SMD -0.02, 95% CI (-0.34, 0.30), p = 0.90), Vd (MD -3.89, 95% CI (-11.17, 3.38), p = 0.29), CL (MD -0.13, 95%CI (-0.88, 0.61), p = 0.72), and MRT (MD 1.89, 95% CI (-0.03, 3.81), p = 0.05) between diabetic and nondiabetic patients with tuberculosis. CONCLUSION: Diabetes mellitus increased the Tmax of rifampicin without further impact on other rifampicin pharmacokinetic parameters such as Cmax, AUC0-24, Vd, CL and MRT. Early therapeutic drug monitoring of rifampicin is necessary for diabetic tuberculosis patients.