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

M. Cevik; A. Sturdy; A. E. Maraolo; B. G.J. Dekkers; O. W. Akkerman; S. H. Gillespie

doi:10.5588/ijtld.23.0507

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

M. Cevik, A. Sturdy, A. E. Maraolo, B. G.J. Dekkers, O. W. Akkerman, S. H. Gillespie

Research output: Contribution to journal › Article › peer-review

Abstract

OBJECTIVES 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.
METHODS We performed a systematic review and meta-analysis through searches of major databases from 1946 to 6 July 2023. PROSPERO (CRD42022323566).
RESULTS 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 (T_max) was significantly prolonged in patients with DM compared with non-DM patients. We found no significant differences for RIF C_max, area under the curve (AUC) 0-24 or drug concentration at 2 h (C2h), INH C2h, PZA C2h, PZA T_max, and EMB T_max. Although RIF C2h was slightly reduced in patients with TB-DM, this finding was not statistically significant.
CONCLUSIONS 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.

Original language	English
Pages (from-to)	454-460
Number of pages	7
Journal	International Journal of Tuberculosis and Lung Disease
Volume	28
Issue number	9
DOIs	https://doi.org/10.5588/ijtld.23.0507
Publication status	Published - 1 Sept 2024

Keywords

DM
PK
Drug treatment
Meta-analysis
Tuberculosis

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.5588/ijtld.23.0507

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title = "A systematic review on the effect of diabetes mellitus on the pharmacokinetics of TB drugs",

abstract = "OBJECTIVES 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. METHODS We performed a systematic review and meta-analysis through searches of major databases from 1946 to 6 July 2023. PROSPERO (CRD42022323566). RESULTS 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. CONCLUSIONS 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.",

keywords = "DM, PK, Drug treatment, Meta-analysis, Tuberculosis",

author = "M. Cevik and A. Sturdy and Maraolo, {A. E.} and Dekkers, {B. G.J.} and Akkerman, {O. W.} and Gillespie, {S. H.}",

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doi = "10.5588/ijtld.23.0507",

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T1 - A systematic review on the effect of diabetes mellitus on the pharmacokinetics of TB drugs

AU - Cevik, M.

AU - Sturdy, A.

AU - Maraolo, A. E.

AU - Dekkers, B. G.J.

AU - Akkerman, O. W.

AU - Gillespie, S. H.

PY - 2024/9/1

Y1 - 2024/9/1

N2 - OBJECTIVES 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. METHODS We performed a systematic review and meta-analysis through searches of major databases from 1946 to 6 July 2023. PROSPERO (CRD42022323566). RESULTS 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. CONCLUSIONS 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.

AB - OBJECTIVES 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. METHODS We performed a systematic review and meta-analysis through searches of major databases from 1946 to 6 July 2023. PROSPERO (CRD42022323566). RESULTS 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. CONCLUSIONS 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.

KW - DM

KW - PK

KW - Drug treatment

KW - Meta-analysis

KW - Tuberculosis

U2 - 10.5588/ijtld.23.0507

DO - 10.5588/ijtld.23.0507

M3 - Article

C2 - 39188008

AN - SCOPUS:85202550486

SN - 1027-3719

VL - 28

SP - 454

EP - 460

JO - International Journal of Tuberculosis and Lung Disease

JF - International Journal of Tuberculosis and Lung Disease

IS - 9

ER -

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

Abstract

Keywords

UN SDGs

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