Therapeutic drug monitoring in patients with tuberculosis and concurrent medical problems

Märtson, Anne-Grete; Burch, Gena M.; Ghimire, Samiksha; Alffenaar, Jan‐Willem C.; Peloquin, Charles A.

doi:10.1080/17425255.2021.1836158

Cited by 38 publications

(143 citation statements)

References 176 publications

(196 reference statements)

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“…EMB's efficacy is predicted by Cmax/MIC and by AUC/MIC. 34 The most serious toxicity of EMB is optic neuritis and is dose-related, and which is consistent with EMB delivery to the CNS. 20,[31][32][33] Screening of acuity and color vision prior to and during treatment is essential, and EMB should be discontinued as soon as this complication is suspected.…”

Section: Ethambutolmentioning

confidence: 61%

“…33,34 RIF has complex absorption involving the hepatic organic anion transporter SLCO1B1. 33,34 RIF is metabolized by hepatic esterases, possibly arylacetamide deacetylase (AADAC), primarily to the partially active 25-O-desacetyl-rifampin. 33 Auto-induction of non-cytochrome P450 pathways reduces RIF's AUC by 30-40% over the first 2 weeks of treatment.…”

Section: Rifampinmentioning

confidence: 99%

“…33 PZA's efficacy is predicted by AUC/MIC. 34 DILI is the main concern with PZA. Current guidelines do not recommend reintroducing PZA after a severe episode of DILI.…”

Section: Pyrazinamidementioning

confidence: 99%

“…Most mutations in the rpoB gene associated with RIF resistance also produce RBN resistance. 20,[31][32][33][34] Some controversy exists as to whether "RIFresistant, RBN-susceptible" isolates can be effectively treated with RBN, since clinical experience is severely limited. RBN absorption is not significantly affected by food.…”

Section: Alternative Drugsmentioning

confidence: 99%

“…C max values with the typical 300 mg daily dose above 0.45 mcg/ml are associated with better clinical outcomes. [32][33][34] RBN does accumulate in aveolar macrophages. 33 Penetration data into caseum are not available.…”

Section: Alternative Drugsmentioning

confidence: 99%

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The Treatment of Tuberculosis

Peloquin

Davies

2021

Clin Pharma and Therapeutics

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Tuberculosis (TB) remains a leading cause of infectious death worldwide, and poverty is a major driver. Clinically, TB presents as “latent” TB and active TB disease, and the treatment for each is different. TB drugs can display “early bactericidal activity (EBA)” and / or “sterilizing activity” (clearing persisters). Isoniazid is excellent at the former, and rifampin is excellent at the latter. Pyrazinamide and ethambutol complete the first‐line regimen for drug‐susceptible TB, each playing a specific role. Drug‐resistant TB is an increasing concern, being met, in part, with repurposed drugs (including moxifloxacin, levofloxacin, linezolid, clofazimine, and beta‐lactams) and new drugs (including bedaquiline, pretomanid, and delamanid). One challenge is to select drugs without overlapping adverse drug reaction profiles. QTc interval prolongation is one such concern, but to date, it has been manageable. Drug penetration into organism sanctuaries, such as the central nervous system, bone, and pulmonary TB cavities remain important challenges. The pharmacodynamics of most TB drugs can be described by the area under the curve (AUC) divided by the minimal inhibitory concentration (MIC). The hollow fiber infection model (HFIM) and various animal models (especially mouse and macaque) allow for sophisticated pharmacokinetic/pharmacodynamic experiments. These experiments may hasten the selection of the most potent, shortest possible regimens to treat even extremely drug resistant TB. These findings can be translated to humans by optimizing drug exposure in each patient, using therapeutic drug monitoring and dose individualization.

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Section: Ethambutolmentioning

confidence: 61%

Section: Rifampinmentioning

confidence: 99%

“…33 PZA's efficacy is predicted by AUC/MIC. 34 DILI is the main concern with PZA. Current guidelines do not recommend reintroducing PZA after a severe episode of DILI.…”

Section: Pyrazinamidementioning

confidence: 99%

Section: Alternative Drugsmentioning

confidence: 99%

Section: Alternative Drugsmentioning

confidence: 99%

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The Treatment of Tuberculosis

Peloquin

Davies

2021

Clin Pharma and Therapeutics

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Diagnostic Accuracy of Therapeutic Drug Monitoring During Tuberculosis Treatment

Anderson

Vinnard

2022

The Journal of Clinical Pharma

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Patients with tuberculosis (TB) coinfected with HIV are more likely to have low blood concentrations of the first‐line anti‐TB drugs (associated with poor outcomes). Therapeutic drug monitoring (TDM) is recommended for certain patient populations with TB at increased risk for a poor outcome. Our objective was to estimate the diagnostic accuracy of a 2‐hour TDM serum sample for the first‐line anti‐TB drugs among patients with HIV/TB and evaluate the information gained by an additional 6‐hour sample. We created a virtual (n = 1000) HIV/TB patient population and performed pharmacokinetic simulations using published population models for isoniazid, rifampin, pyrazinamide, and ethambutol. We performed receiver operating characteristic analysis to compare the diagnostic performance of a single 2‐hour serum sample with samples obtained at 2 and 6 hours after dosing. The sensitivity of a single 2‐hour serum concentration to identify patients with HIV/TB with adequate serum exposures was lowest for rifampin (54.9%; 95%CI, 50.79%‐59.41%) and highest for ethambutol (70.8%; 95%CI, 66.06%‐72.61%) for maximum concentration (Cmax) targets. Diagnostic accuracy of a single 2‐hour serum sample for the area under the concentration‐time curve (AUC) from time 0 to 24 hours target was highest for isoniazid (93%; 95%CI, 90.9%‐94.1%) and lowest for pyrazinamide (66.3%; 95%CI, 62.6%‐70.0%). In summary, the diagnostic performance of TDM for Cmax and AUC from time 0 to 24 hours targets demonstrated variability across the first‐line anti‐TB drugs. The addition of a 6‐hour serum sample led to the highest statistically significant improvement (P < .001) and highest increase in diagnostic accuracy (area under the receiver operating characteristic curve) for rifampin for Cmax and AUC. The other first‐line drugs had modest/negligible increases in diagnostic accuracy.

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Therapeutic drug monitoring in tuberculosis

Sarkar,

Sarkar

2024

Eur J Clin Pharmacol

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Therapeutic drug monitoring in patients with tuberculosis and concurrent medical problems

Cited by 38 publications

References 176 publications

The Treatment of Tuberculosis

The Treatment of Tuberculosis

Diagnostic Accuracy of Therapeutic Drug Monitoring During Tuberculosis Treatment

Therapeutic drug monitoring in tuberculosis

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