Mode of Action, Biotransformation and Pharmacokinetics of Antituberculosis Drugs in Animals and Man

Iwainsky, H

doi:10.1007/978-3-642-72873-0_6

Cited by 23 publications

(23 citation statements)

References 341 publications

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“…Similar low sensitivity (42·6%) of detecting OFX PR strains was also found in conventional DST. Despite these PR strains possessing susceptible MICs, ineffective drug treatment may still result from relative low peak serum concentration levels of the drug (Heifets 1991; Iwainsky 1998). For OFX, as the critical inhibitory concentration (3μg ml −1 ) (Kam et al.…”

Section: Discussionmentioning

confidence: 99%

Usefulness of resistant gene markers for predicting treatment outcome on second-line anti-tuberculosis drugs

Leung

Yip

Yeung

et al. 2010

Journal of Applied Microbiology

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Aim: Mutations in rrs [nucleotide (nt) 1401], gyrA gene (codons 90, 91 or 94), tlyA, ethA and thyA genes of Mycobacterium tuberculosis (MTB) were evaluated for their usefulness in predicting treatment outcome of kanamycin (KM), capreomycin (CPM), ofloxacin (OFX), ethionamide (ETH) and para‐aminosalicylic acid (PAS). Methods and Results: DNA sequence analyses of these genes were performed against 188 MTB isolates obtained from patients put on second‐line anti‐TB drugs (SLDs) with well‐documented clinical history and treatment outcome. Mutations in rrs and gyrA have 100% positive predictive value (PPV) in predicting treatment failure for KM and OFX, while 88·9 and 80% were obtained, respectively, when tlyA and rrs mutations were considered in CPM. For ETH and PAS, the PPV of using ethA and thyA mutations to predict treatment failure was 82·5 and 89·3%, respectively. Conclusions: Our study demonstrated high specificities of gene mutations in predicting poor treatment outcome; however, further technical advancement is required to make the molecular detection of resistances to other SLDs feasible in clinical laboratories. Significance and Impact of the Study: This is the first study to correlate different polymorphisms of major SLD resistance gene markers with predicted treatment outcome, using an international set of well‐documented clinical MTB strains.

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Section: Discussionmentioning

confidence: 99%

Usefulness of resistant gene markers for predicting treatment outcome on second-line anti-tuberculosis drugs

Leung

Yip

Yeung

et al. 2010

Journal of Applied Microbiology

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“…INH and RFP, whose susceptibility testing results are fairly reliable, show a peak serum concentration over 100-times higher than the MIC, and it is certainly possible to maintain them at a fairly high concentration in the lesions throughout the treatment, unless the patient interrupts drug intake ( fig. 6) [27,28]. Conversely, peak serum levels of cycloserine, EMB, ciprofloxacin, ofloxacin and ETH are closer to MICs ( fig.…”

Section: Anti-tb Drug-susceptibility Testing Sj Kimmentioning

confidence: 96%

“…Development of drug resistance by selective multiplication of resistant mutants existing in a wild bacillary population is determined by the initial size of actively multiplying organisms in the lesions, the drug exposure time and the drug concentration [4,24,26,27]. The absorption, the diffusion into the lesions and the maintenance level of a drug are all important factors for the emergence of drug resistance.…”

Section: Anti-tb Drug-susceptibility Testing Sj Kimmentioning

confidence: 99%

Drug-susceptibility testing in tuberculosis: methods and reliability of results

Kim¹

2005

European Respiratory Journal

250

191

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The demand for reliable drug-susceptibility testing (DST) increases with the expansion of antituberculosis drug-resistance surveillance, and with the need for an appropriate treatment of multidrug-resistant tuberculosis, whose incidence gradually increases in many parts of the world. However, the reliability of DST results obtained through widely used methods does not meet acceptable levels, except for DST to isoniazid and rifampicin.In general, susceptibility results are highly predictable, while resistance results show low predictive values when the resistance prevalence is ,10%. Poor reliability stems from a weak correlation with clinical response and a low reproducibility due to the poor standardisation of the complex and fragile test procedures. Therefore, in vitro criteria of resistance for susceptibility testing should be carefully determined with representative clinical samples of Mycobacterium tuberculosis isolated from patients never treated with any antituberculosis drug, and from patients having failed treatment with a regimen containing the tested drug; DST should then be carefully standardised to obtain reproducible results.The critical concentration of some drugs is close to the minimal inhibitory concentration for wild susceptible strains and, thus, drug-susceptibility testing is prone to yield poorly reproducible results. These issues call for physicians' attention when using the results from drug-susceptibility testing for case management.

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“…Although the brain penetrance of D-cycloserine is not high, it can nonetheless infiltrate the blood-brain barrier, exerting a peak effect 1 h after intraperitoneal administration (Peterson, 1992). D-cycloserine shows dose-dependent elimination (higher elimination rates with lower doses) and a half-life of 7–15 h in humans and 23 min in mice (lwainsky, 1988; Wlaz et al, 1994). …”

Section: Potential Treatments For Asdmentioning

confidence: 99%

Autism spectrum disorder causes, mechanisms, and treatments: focus on neuronal synapses

Won¹,

Mah²,

Kim³

2013

Front. Mol. Neurosci.

170

137

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Autism spectrum disorder (ASD) is a group of developmental disabilities characterized by impairments in social interaction and communication and restricted and repetitive interests/behaviors. Advances in human genomics have identified a large number of genetic variations associated with ASD. These associations are being rapidly verified by a growing number of studies using a variety of approaches, including mouse genetics. These studies have also identified key mechanisms underlying the pathogenesis of ASD, many of which involve synaptic dysfunctions, and have investigated novel, mechanism-based therapeutic strategies. This review will try to integrate these three key aspects of ASD research: human genetics, animal models, and potential treatments. Continued efforts in this direction should ultimately reveal core mechanisms that account for a larger fraction of ASD cases and identify neural mechanisms associated with specific ASD symptoms, providing important clues to efficient ASD treatment.

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Mode of Action, Biotransformation and Pharmacokinetics of Antituberculosis Drugs in Animals and Man

Cited by 23 publications

References 341 publications

Usefulness of resistant gene markers for predicting treatment outcome on second-line anti-tuberculosis drugs

Usefulness of resistant gene markers for predicting treatment outcome on second-line anti-tuberculosis drugs

Drug-susceptibility testing in tuberculosis: methods and reliability of results

Autism spectrum disorder causes, mechanisms, and treatments: focus on neuronal synapses

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