The challenges of pharmacokinetic variability of first-line anti-TB drugs

Daniel, B; Ramachandran, Geetha; Swaminathan, Soumya

doi:10.1080/17512433.2017.1246179

Cited by 24 publications

(14 citation statements)

References 115 publications

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“…The development of cancer biology and drug discovery has identified thousands of therapeutics, many of which unfortunately failed to further develop into clinical drugs because of unfavorable druggability, such as poor solubility, low-membrane permeability, and instability in biological fluids. Meanwhile, the PK variations among different drugs would result in unwanted toxicity and variable therapeutic effects 26 , 27 . On this account, NMs have been demonstrated with the capacities of improving drug solubility and stability, as well as promoting the penetration through various biological barriers.…”

Section: Nanotechnology-based Codeliverymentioning

confidence: 99%

Nanotechnology-based combination therapy for overcoming multidrug-resistant cancer

Zhang

Liu

Cui

et al. 2017

Cancer Biology & Medicine

102

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Multidrug resistance (MDR) is a major obstacle to successful cancer treatment and is crucial to cancer metastasis and relapse. Combination therapy is an effective strategy for overcoming MDR. However, the different pharmacokinetic (PK) profiles of combined drugs often undermine the combination effect in vivo, especially when greatly different physicochemical properties (e.g., those of macromolecules and small drugs) combine. To address this issue, nanotechnology-based codelivery techniques have been actively explored. They possess great advantages for tumor targeting, controlled drug release, and identical drug PK profiles. Thus, a powerful tool for combination therapy is provided, and the translation from in vitro to in vivo is facilitated. In this review, we present a summary of various combination strategies for overcoming MDR and the nanotechnology-based combination therapy.

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Section: Nanotechnology-based Codeliverymentioning

confidence: 99%

Nanotechnology-based combination therapy for overcoming multidrug-resistant cancer

Zhang

Liu

Cui

et al. 2017

Cancer Biology & Medicine

102

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“…The recommended regimen consists of a 2-month intensive phase with all four FLDs, and a 4-month continuation phase with RIF and INH only [7]. Despite the utilization of weight-banded dosing, high pharmacokinetic (PK) variability has been reported for the FLDs in studies investigating the PK of these drugs [8][9][10]. The hollow-fibre infection model and murine model conducted with the four FLDs showed that their effectiveness is best reflected by the area under the concentration-time curve (AUC)/minimum inhibitory concentration (MIC) ratio [9,[11][12][13].…”

Section: Introductionmentioning

confidence: 99%

A Systematic Review on the Effect of HIV Infection on the Pharmacokinetics of First-Line Tuberculosis Drugs

et al. 2018

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Introduction Contrasting findings have been published regarding the effect of human immunodeficiency virus (HIV) on tuberculosis (TB) drug pharmacokinetics (PK). Objectives The aim of this systematic review was to investigate the effect of HIV infection on the PK of the first-line TB drugs (FLDs) rifampicin, isoniazid, pyrazinamide and ethambutol by assessing all published literature. Methods Searches were performed in MEDLINE (through PubMed) and EMBASE to find original studies evaluating the effect of HIV infection on the PK of FLDs. The included studies were assessed for bias and clinical relevance. PK data were extracted to provide insight into the difference of FLD PK between HIV-positive and HIV-negative TB patients. This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement and its protocol was registered at PROSPERO (registration number CRD42017067250). Results Overall, 27 studies were eligible for inclusion. The available studies provide a heterogeneous dataset from which consistent results could not be obtained. In both HIV-positive and HIV-negative TB groups, rifampicin (13 of 15) and ethambutol (4 of 8) peak concentration (C max) often did not achieve the minimum reference values. More than half of the studies (11 of 20) that included both HIV-positive and HIV-negative TB groups showed statistically significantly altered FLD area under the concentration-time curve and/or C max for at least one FLD. Conclusions HIV infection may be one of several factors that reduce FLD exposure. We could not make general recommendations with respect to the role of dosing. There is a need for consistent and homogeneous studies to be conducted.

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“…Furthermore, in our TB patients treated under direct observation (DOT), moxifloxacin PK variability in plasma was found to be ninefold on 400 mg/day [ 36 ]. The PK of all anti-tuberculosis drugs could be affected by TB disease activity (wasting, loss of lean body mass, fat and serum proteins), HIV, diabetes or drug–drug interactions [ 37 , 38 ]. The PK interaction between rifampicin and moxifloxacin is well known [ 39 , 40 ].…”

Section: Discussionmentioning

confidence: 99%

The Role of Fluoroquinolones in the Treatment of Tuberculosis in 2019

Pranger

Werf

Kosterink

et al. 2019

Drugs

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The inability to use powerful antituberculosis drugs in an increasing number of patients seems to be the biggest threat towards global tuberculosis (TB) elimination. Simplified, shorter and preferably less toxic drug regimens are being investigated for pulmonary TB to counteract emergence of drug resistance. Intensified regimens with high-dose anti-TB drugs during the first weeks of treatment are being investigated for TB meningitis to increase the survival rate among these patients. Moxifloxacin, gatifloxacin and levofloxacin are seen as core agents in case of resistance or intolerance against first-line anti-TB drugs. However, based on their pharmacokinetics (PK) and pharmacodynamics (PD), these drugs are also promising for TB meningitis and might perhaps have the potential to shorten pulmonary TB treatment if dosing could be optimized. We prepared a comprehensive summary of clinical trials investigating the outcome of TB regimens based on moxifloxacin, gatifloxacin and levofloxacin in recent years. In the majority of clinical trials, treatment success was not in favour of these drugs compared to standard regimens. By discussing these results, we propose that incorporation of extended PK/PD analysis into the armamentarium of drug-development tools is needed to clarify the role of moxifloxacin, gatifloxacin and levofloxacin for TB, using the right dose. In addition, to prevent failure of treatment or emergence of drug-resistance, PK and PD variability advocates for concentration-guided dosing in patients at risk for too low a drug-exposure.

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The challenges of pharmacokinetic variability of first-line anti-TB drugs

Cited by 24 publications

References 115 publications

Nanotechnology-based combination therapy for overcoming multidrug-resistant cancer

Nanotechnology-based combination therapy for overcoming multidrug-resistant cancer

A Systematic Review on the Effect of HIV Infection on the Pharmacokinetics of First-Line Tuberculosis Drugs

The Role of Fluoroquinolones in the Treatment of Tuberculosis in 2019

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