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

Abstract

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.

Keywords: Diabetes mellitus; Pharmacokinetic; Rifampicin; Tuberculosis.