A Simple and Rapid Liquid Chromatography Method for Determination of Levofloxacin in Plasma

Kumar, A. K. Hemanth; Sudha, Vasudevan; Ramachandran, Geetha

doi:10.3126/saarctb.v14i1.17726

Cited by 3 publications

(2 citation statements)

References 17 publications

(23 reference statements)

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“…The mobile phase consisted of a mixture of phosphate buffer and acetonitrile. The retention time of LFX was 1.8 min (30). The method for estimation of PZA involved deproteinization of plasma with parahydroxy benzaldehyde and trifluoroacetic acid and was analysis using a reversed-phase C 8 column and UV detector set at 267 nm.…”

Section: Methodsmentioning

confidence: 99%

Pharmacokinetics of Second-Line Antituberculosis Drugs in Children with Multidrug-Resistant Tuberculosis in India

Kumar

Thiruvengadam

et al. 2018

Antimicrob Agents Chemother

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We studied the pharmacokinetics of levofloxacin (LFX), pyrazinamide (PZA), ethionamide (ETH), and cycloserine (CS) in children with multidrug-resistant tuberculosis (MDR-TB) who were being treated according to the Revised National TB Control Programme (RNTCP) guidelines in India. This observational, pharmacokinetic study was conducted in 25 children with MDR-TB at the Sarojini Naidu Medical College, Agra, India, who were being treated with a 24-month daily regimen. Serial blood samples were collected after directly observed administration of drugs. Estimations of plasma LFX, PZA, ETH, and CS were undertaken according to validated methods by high-performance liquid chromatography. Adverse events were noted at 6 months of treatment. The peak concentration () of LFX was significantly higher in female than male children (11.5 μg/ml versus 7.3 μg/ml; = 0.017). Children below 12 years of age had significantly higher ETH exposure (area under the concentration-time curve from 0 to 8 h [AUC]) than those above 12 years of age (17.5 μg/ml · h versus 9.4 μg/ml; = 0.030). Multiple linear regression analysis showed significant influence of gender on of ETH and age on and AUC of CS. This is the first and only study from India reporting on the pharmacokinetics of LFX, ETH, PZA, and CS in children with MDR-TB treated in the Government of India program. More studies on the safety and pharmacokinetics of second-line anti-TB drugs in children with MDR-TB from different settings are required.

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Section: Methodsmentioning

confidence: 99%

Pharmacokinetics of Second-Line Antituberculosis Drugs in Children with Multidrug-Resistant Tuberculosis in India

Kumar

Thiruvengadam

et al. 2018

Antimicrob Agents Chemother

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“…The retention times of LFX and MFX were 1.8 and 4.6 minutes respectively (8,9). Plasma INH and PZA were estimated simultaneously by extraction using parahydrobenzaldehyde and trifluoro acetic acid.…”

Section: Drug Estimationsmentioning

confidence: 99%

Pharmacokinetics of anti-tuberculosis drugs in multidrug resistant tuberculosis patients in India

Hemanth

Natarajan

Thiruvengadam

et al. 2020

Preprint

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Programmatic Management of multidrug resistant tuberculosis (MDR TB) services were introduced in the Indian TB control programme in 2007. A pharmacokinetic (PK) study of drugs used to treat MDR TB, namely levofloxacin (LFX), ethionamide (ETH), cycloserine (CS), pyrazinamide (PZA), moxifloxacin (MFX) and isoniazid (INH) was undertaken in adult MDR TB patients treated according to the prevailing guidelines in India. Factors influencing drug PK and end-of-intensive phase (IP) status were also determined. We recruited 350 MDR TB patients receiving anti-TB treatment (ATT) in the Indian Government programme in south India. At steady state, serial blood samples were collected, after supervised drug administration. Status at end of IP was noted from the programme records. Of the 303 patients for whom end-of-IP status was known, 214 were culture negative (responders), while 45 patients were either culture positive or required change of regimen or had died before completion of IP (non-responders). The median Cmax (2.0 vs 2.9µg/ml; p = 0.005) and AUC0-12 (12.2 vs 17.0µg/ml.h; p = 0.002) of ETH were significantly lower in non-responders than responders at IP. In multivariate logistic regression analysis, after excluding defaulters and adjusting for confounders, AUC0-12 of ETH significantly influenced end-of-IP status (aOR - 1.065; 95% CI: 1.001 - 1.134; p = 0.047). Drug doses used currently in the programme produced optimal drug concentrations in majority of patients. ETH played a major role in the MDR TB combination regimen and was a key determinant of end-of-IP status.

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Pharmacokinetics of anti-TB drugs in children and adolescents with drug-resistant TB: a multicentre observational study from India

Agibothu Kupparam,

Shah,

Chandrasekaran

et al. 2024

Journal of Antimicrobial Chemotherapy

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Background Drug-resistant tuberculosis (DR-TB) is one of the challenging forms of TB to treat, not only in adults but also in children and adolescents. Further, there is a void in the treatment strategy exclusively for children due to various reasons, including paucity of pharmacokinetic (PK) data on anti-TB drugs across the globe. In this context, the present study aimed at assessing the PK of some of the anti-TB drugs used in DR-TB treatment regimens. Method A multicentre observational study was conducted among DR-TB children and adolescents (n = 200) aged 1–18 years (median: 12 years; IQR: 9–14) treated under programmatic settings in India. Steady-state PK (intensive: n = 89; and sparse: n = 111) evaluation of moxifloxacin, levofloxacin, cycloserine, ethionamide, rifampicin, isoniazid and pyrazinamide was carried out by measuring plasma levels using HPLC methods. Results In the study population, the frequency of achieving peak plasma concentrations ranged between 13% (for rifampicin) to 82% (for pyrazinamide), whereas the frequency of suboptimal peak concentration for pyrazinamide, cycloserine, moxifloxacin, levofloxacin and rifampicin was 15%, 19%, 29%, 41% and 74%, respectively. Further, the frequency of supratherapeutic levels among patients varied between 3% for pyrazinamide and 60% for isoniazid. In the below-12 years age category, the median plasma maximum concentration and 12 h exposure of moxifloxacin were significantly lower than that of the above-12 years category despite similar weight-adjusted dosing. Conclusions Age significantly impacted the plasma concentration and exposure of moxifloxacin. The observed frequencies of suboptimal and supratherapeutic concentrations underscore the necessity for dose optimization and therapeutic drug monitoring in children and adolescents undergoing DR-TB treatment.

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A Simple and Rapid Liquid Chromatography Method for Determination of Levofloxacin in Plasma

Cited by 3 publications

References 17 publications

Pharmacokinetics of Second-Line Antituberculosis Drugs in Children with Multidrug-Resistant Tuberculosis in India

Pharmacokinetics of Second-Line Antituberculosis Drugs in Children with Multidrug-Resistant Tuberculosis in India

Pharmacokinetics of anti-tuberculosis drugs in multidrug resistant tuberculosis patients in India

Pharmacokinetics of anti-TB drugs in children and adolescents with drug-resistant TB: a multicentre observational study from India

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