Dose optimisation of first-line tuberculosis drugs using therapeutic drug monitoring in saliva: feasible for rifampicin, not for isoniazid

Elsen, Simone H.J. van den; Akkerman, Onno W.; Wessels, Mireille; Jongedijk, Erwin M; Ghimire, Samiksha; Werf, Tjip S van der; Bolhuis, Mathieu S.; Touw, Daan; Alffenaar, Jan‐Willem C.

doi:10.1183/13993003.00803-2020

Cited by 8 publications

(12 citation statements)

References 14 publications

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“…114 Limited intraindividual variability of linezolid and less invasive sampling techniques (e.g., dried blood spot or saliva sampling) support the feasibility of linezolid TDM. 31,113,115 A shift from empirical dose adjustment-assuming dose-exposure linearity-towards MIPD seems promising for linezolid, as it facilitates considering nonlinear PK and more complex targets like AUC/MIC.…”

Section: Linezolidmentioning

confidence: 99%

From Therapeutic Drug Monitoring to Model‐Informed Precision Dosing for Antibiotics

Wicha

Märtson

Nielsen

et al. 2021

Clin Pharma and Therapeutics

170

159

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(ISAP), the PK/PD study group of the European Society of Clinical Microbiology, Infectious Diseases (EPASG) Therapeutic drug monitoring (TDM) and model-informed precision dosing (MIPD) have evolved as important tools to inform rational dosing of antibiotics in individual patients with infections. In particular, critically ill patients display altered, highly variable pharmacokinetics and often suffer from infections caused by less susceptible bacteria. Consequently, TDM has been used to individualize dosing in this patient group for many years. More recently, there has been increasing research on the use of MIPD software to streamline the TDM process, which can increase the flexibility and precision of dose individualization but also requires adequate model validation and re-evaluation of existing workflows. In parallel, new minimally invasive and noninvasive technologies such as microneedle-based sensors are being developed, which-together with MIPD software-have the potential to revolutionize how patients are dosed with antibiotics. Nonetheless, carefully designed clinical trials to evaluate the benefit of TDM and MIPD approaches are still sparse, but are critically needed to justify the implementation of TDM and MIPD in clinical practice. The present review summarizes the clinical pharmacology of antibiotics, conventional TDM and MIPD approaches, and evidence of the value of TDM/MIPD for aminoglycosides, beta-lactams, glycopeptides, and linezolid, for which precision dosing approaches have been recommended.

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Section: Linezolidmentioning

confidence: 99%

From Therapeutic Drug Monitoring to Model‐Informed Precision Dosing for Antibiotics

Wicha

Märtson

Nielsen

et al. 2021

Clin Pharma and Therapeutics

170

159

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“…Except for Panjasawatwong et al which employed blood and cerebrospinal fluid (CSF) sampling in the Vietnamese pediatric TB meningitis population, all the other studies employed blood sampling for isoniazid level estimation. Unlike many other ATT, therapeutic drug monitoring (TDM) of isoniazid by saliva sample is not a viable alternative to blood sample [ 41 ]. Most of the isoniazid PopPK studies with NAT2 genotype/SNP have been reported from high TB burden World Health Organization (WHO) regions of South-East Asia and Africa (Asian, n = 5; African n = 6).…”

Section: Discussionmentioning

confidence: 99%

Influence of N-acetyltransferase 2 (NAT2) genotype/single nucleotide polymorphisms on clearance of isoniazid in tuberculosis patients: a systematic review of population pharmacokinetic models

Thomas

Raju

Chaithra

et al. 2022

Eur J Clin Pharmacol

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Purpose Significant pharmacokinetic variabilities have been reported for isoniazid across various populations. We aimed to summarize population pharmacokinetic studies of isoniazid in tuberculosis (TB) patients with a specific focus on the influence of N-acetyltransferase 2 (NAT2) genotype/single-nucleotide polymorphism (SNP) on clearance of isoniazid. Methods A systematic search was conducted in PubMed and Embase for articles published in the English language from inception till February 2022 to identify population pharmacokinetic (PopPK) studies of isoniazid. Studies were included if patient population had TB and received isoniazid therapy, non-linear mixed effects modelling, and parametric approach was used for building isoniazid PopPK model and NAT2 genotype/SNP was tested as a covariate for model development. Results A total of 12 articles were identified from PubMed, Embase, and hand searching of articles. Isoniazid disposition was described using a two-compartment model with first-order absorption and linear elimination in most of the studies. Significant covariates influencing the pharmacokinetics of isoniazid were NAT2 genotype, body weight, lean body weight, body mass index, fat-free mass, efavirenz, formulation, CD4 cell count, and gender. Majority of studies conducted in adult TB population have reported a twofold or threefold increase in isoniazid clearance for NAT2 rapid acetylators compared to slow acetylators. Conclusion The variability in disposition of isoniazid can be majorly attributed to NAT2 genotype. This results in a trimodal clearance pattern with a multi-fold increase in clearance of NAT2 rapid acetylators compared to slow acetylators. Further studies exploring the generalizability/adaptability of developed PopPK models in different clinical settings are required.

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“… 14 , 16 Saliva offers an alternative approach, but a recent publication highlighted issues with highly variable saliva–serum concentrations. 17 …”

Section: Introductionmentioning

confidence: 99%

“…Novel approaches for monitoring TB treatment adherence include the use of hair samples or saliva as a testing matrix. − Hair can provide a snapshot of historic drug use (therapeutic or illicit), depending on the hair length and the stability of the drugs. However, it presents challenges with external contamination and/or effect of hair treatments ( e.g.…”

Section: Introductionmentioning

confidence: 99%

“…, hair dye), which can lead to false positive or negative results, respectively . Additionally, the quantitative potential of this matrix is poor, and publications have highlighted how failing to take historic medication uptake into consideration can result in false positive results or falsely high measurement of drug levels in hair samples. , Saliva offers an alternative approach, but a recent publication highlighted issues with highly variable saliva–serum concentrations …”

Section: Introductionmentioning

confidence: 99%

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Potential to Use Fingerprints for Monitoring Therapeutic Levels of Isoniazid and Treatment Adherence

et al. 2022

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A fingerprint offers a convenient, noninvasive sampling matrix for monitoring therapeutic drug use. However, a barrier to widespread adoption of fingerprint sampling is the fact that the sample volume is uncontrolled. Fingerprint samples ( n = 140) were collected from patients receiving the antibiotic isoniazid as part of their treatment, as well as from a drug-naive control group ( n = 50). The fingerprint samples were analyzed for isoniazid (INH) and acetylisoniazid (AcINH), using liquid chromatography high-resolution mass spectrometry. The data set was analyzed retrospectively for metabolites known to be present in eccrine sweat. INH or AcINH was detected in 89% of the fingerprints collected from patients and in 0% of the fingerprints collected from the control group. Metabolites lysine, ornithine, pyroglutamic acid, and taurine were concurrently detected alongside INH/AcINH and were used to determine whether the fingerprint sample was sufficient for testing. Given a sufficient sample volume, the fingerprint test for INH use has sensitivity, specificity, and accuracy of 100%. Normalization to taurine was found to reduce intradonor variability. Fingerprints are a novel and noninvasive approach to monitor INH therapy. Metabolites can be used as internal markers to demonstrate a sufficient sample volume for testing and reduce intradonor variability.

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Dose optimisation of first-line tuberculosis drugs using therapeutic drug monitoring in saliva: feasible for rifampicin, not for isoniazid

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Cited by 8 publications

References 14 publications

From Therapeutic Drug Monitoring to Model‐Informed Precision Dosing for Antibiotics

From Therapeutic Drug Monitoring to Model‐Informed Precision Dosing for Antibiotics

Influence of N-acetyltransferase 2 (NAT2) genotype/single nucleotide polymorphisms on clearance of isoniazid in tuberculosis patients: a systematic review of population pharmacokinetic models

Potential to Use Fingerprints for Monitoring Therapeutic Levels of Isoniazid and Treatment Adherence

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