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

Kumar, A. K. Hemanth; Kumar, Ashish; Thiruvengadam, Kannan; Bhatia, Rakesh; Agarwal, Dipti; Kumar, Santosh; Dayal, Rajeshwar; Sk, Singh; Ramachandran, Geetha

doi:10.1128/aac.02410-17

Cited by 16 publications

(5 citation statements)

References 32 publications

(30 reference statements)

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“…This typical range seems to be applicable to children as well. Kumar et al recently reported an average plasma concentration of 32 mg/liter in children with MDR-TB after receiving an average dose of 14 mg/kg (∼500 mg dose), which is in accordance with early studies (21, 22).…”

Section: Discussionsupporting

confidence: 78%

Cycloserine Population Pharmacokinetics and Pharmacodynamics in Patients with Tuberculosis

Alghamdi

Alsultan

Al‐Shaer

et al. 2019

Antimicrob Agents Chemother

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Section: Discussionsupporting

confidence: 78%

Cycloserine Population Pharmacokinetics and Pharmacodynamics in Patients with Tuberculosis

Alghamdi

Alsultan

Al‐Shaer

et al. 2019

Antimicrob Agents Chemother

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“…A published IPDMA of children with successful treatment of MDR-TB showed that cycloserine as a single drug had an aOR of 1.7 (95% CI, 0.9–3.0; 641 children with MDR-TB, of whom 356 [56%] received cycloserine/terizidone) (113). Limited pharmacokinetic data are available on cycloserine (or terizidone) in children, but a recent study of 25 children (only 5 to <12 yr of age) receiving a median of 14.3 mg/kg (range, 10.0–18.0 mg/kg) showed that the maximum concentration of the drug achieved in the plasma after dose administration was similar to the adult target maximum concentration of 20 to 35 mg/L (119). The recommended dose for children of 10 to 20 mg/kg/d seems adequate.…”

Section: Drugs and Drug Classesmentioning

confidence: 99%

“…Our PS-matched IPDMA did not include sufficient numbers of children to allow the formulations of GRADE-based recommendations. Nonetheless, on the basis of a recent IPDMA of 975 children with MDR-TB from 18 countries, recent pharmacokinetic studies in children, and several observational studies showing good outcomes, the recommendations noted on choice of drugs, composition of regimens, and durations of treatment for adults can also be applied to children with MDR-TB (113, 119, 124, 161, 165, 170, 200, 310).…”

Section: Treatment Of Mdr-tb In Special Situationsmentioning

confidence: 99%

Treatment of Drug-Resistant Tuberculosis. An Official ATS/CDC/ERS/IDSA Clinical Practice Guideline

Nahid¹,

Mase²,

Migliori³

et al. 2019

Am J Respir Crit Care Med

329

342

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jointly sponsored this new practice guideline on the treatment of drug-resistant tuberculosis (DR-TB). The document includes recommendations on the treatment of multidrug-resistant TB (MDR-TB) as well as isoniazid-resistant but rifampin-susceptible TB. Methods: Published systematic reviews, meta-analyses, and a new individual patient data meta-analysis from 12,030 patients, in 50 studies, across 25 countries with confirmed pulmonary rifampinresistant TB were used for this guideline. Meta-analytic approaches included propensity score matching to reduce confounding. Each recommendation was discussed by an expert committee, screened for conflicts of interest, according to the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology. Results: Twenty-one Population, Intervention, Comparator, and Outcomes questions were addressed, generating 25 GRADE-based recommendations. Certainty in the evidence was judged to be very low, because the data came from observational studies with significant loss to follow-up and imbalance in background regimens between comparator groups. Good practices in the management of MDR-TB are described. On the basis of the evidence review, a clinical strategy tool for building a treatment regimen for MDR-TB is also provided. Conclusions: New recommendations are made for the choice and number of drugs in a regimen, the duration of intensive and continuation phases, and the role of injectable drugs for MDR-TB. On the basis of these recommendations, an effective all-oral regimen for MDR-TB can be assembled. Recommendations are also provided on the role of surgery in treatment of MDR-TB and for treatment of contacts exposed to MDR-TB and treatment of isoniazid-resistant TB.

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“…The analytical column was Atlantis T3 and the mobile phase was a mixture of phosphate buffer, acetonitrile and isopropyl alcohol. The retention time of CS was 4.8 minutes (11).…”

Section: Methodsmentioning

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

Cited by 16 publications

References 32 publications

Cycloserine Population Pharmacokinetics and Pharmacodynamics in Patients with Tuberculosis

Cycloserine Population Pharmacokinetics and Pharmacodynamics in Patients with Tuberculosis

Treatment of Drug-Resistant Tuberculosis. An Official ATS/CDC/ERS/IDSA Clinical Practice Guideline

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

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