A systematic review on the effect of diabetes mellitus on the pharmacokinetics of TB drugs

Author:

Cevik M.1,Sturdy A.2,Maraolo A.E.3,Dekkers B.G.J.4,Akkerman O.W.5,Gillespie S.H.1,J-W.C. Alffenaar 6

Affiliation:

1. Division of Infection and Global Health Research, School of Medicine, University of St Andrews, Fife, Scotland,

2. Department of Infectious Disease, Faculty of Medicine, Imperial College London, UK;

3. Department of Clinical Medicine and Surgery, Section of Infectious Diseases, University of Naples 'Federico II', Italy;

4. University of Groningen, University Medical Center Groningen, Department of Clinical Pharmacy and Pharmacology, Groningen,

5. University of Groningen, University Medical Center Groningen, Department of Pulmonary Diseases and Tuberculosis, Groningen, University of Groningen, University Medical Center Groningen, Tuberculosis Center Beatrixoord, Haren, the Netherlands;

6. The University of Sydney Institute for Infectious Diseases, Sydney, NSW, School of Pharmacy, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Westmead Hospital, Westmead, NSW, Australia.

Abstract

<sec><title>OBJECTIVES</title>The coexistence of TB and diabetes mellitus (DM) (TB-DM) is associated with an increased risk of treatment failure, death, delayed culture conversion, and drug resistance. Because plasma concentrations may influence clinical outcomes, we evaluated the evidence on the pharmacokinetic (PK) of TB drugs in individuals with DM to guide management.</sec><sec><title>METHODS</title>We performed a systematic review and meta-analysis through searches of major databases from 1946 to 6 July 2023. PROSPERO (CRD42022323566).</sec><sec><title>RESULTS</title>Of 4,173 potentially relevant articles, we identified 16 studies assessing rifampicin (RIF) PK, 9 on isoniazid (INH), 8 on pyrazinamide (PZA), and 3 on ethambutol (EMB). Two studies reported on second-line anti-TB drugs. According to our meta-analysis, RIF time to maximum concentration (Tmax) was significantly prolonged in patients with DM compared with non-DM patients. We found no significant differences for RIF Cmax, area under the curve (AUC) 0–24 or drug concentration at 2 h (C2h), INH C2h, PZA C2h, PZA Tmax, and EMB Tmax. Although RIF C2h was slightly reduced in patients with TB-DM, this finding was not statistically significant.</sec><sec><title>CONCLUSIONS</title>This review comprehensively examines the impact of DM on the PK of TB drugs. We observed significant heterogeneity among the studies. Given the association between lower plasma concentrations and poor clinical outcomes among patients with DM, we recommend a higher dose limit to compensate for the larger body weight of patients with DM.</sec>

Publisher

International Union Against Tuberculosis and Lung Disease

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