{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T19:21:41Z","timestamp":1788895301169,"version":"build-2803163510"},"reference-count":34,"publisher":"American Society for Microbiology","issue":"5","license":[{"start":{"date-parts":[[2018,5,1]],"date-time":"2018-05-01T00:00:00Z","timestamp":1525132800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2018,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            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 (\n            <jats:italic>C<\/jats:italic>\n            <jats:sub>max<\/jats:sub>\n            ) of LFX was significantly higher in female than male children (11.5 \u03bcg\/ml versus 7.3 \u03bcg\/ml;\n            <jats:italic>P<\/jats:italic>\n            = 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\n            <jats:sub>0\u20138<\/jats:sub>\n            ]) than those above 12 years of age (17.5 \u03bcg\/ml \u00b7 h versus 9.4 \u03bcg\/ml;\n            <jats:italic>P<\/jats:italic>\n            = 0.030). Multiple linear regression analysis showed significant influence of gender on\n            <jats:italic>C<\/jats:italic>\n            <jats:sub>max<\/jats:sub>\n            of ETH and age on\n            <jats:italic>C<\/jats:italic>\n            <jats:sub>max<\/jats:sub>\n            and AUC\n            <jats:sub>0\u20138<\/jats:sub>\n            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.\n          <\/jats:p>","DOI":"10.1128\/aac.02410-17","type":"journal-article","created":{"date-parts":[[2018,2,16]],"date-time":"2018-02-16T09:45:28Z","timestamp":1518774328000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":17,"title":["Pharmacokinetics of Second-Line Antituberculosis Drugs in Children with Multidrug-Resistant Tuberculosis in India"],"prefix":"10.1128","volume":"62","author":[{"given":"Agibothu Kupparam","family":"Hemanth Kumar","sequence":"first","affiliation":[{"name":"National Institute for Research in Tuberculosis (ICMR), Chennai, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alok","family":"Kumar","sequence":"additional","affiliation":[{"name":"Sarojini Naidu Medical College, Agra, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thiruvengadam","family":"Kannan","sequence":"additional","affiliation":[{"name":"National Institute for Research in Tuberculosis (ICMR), Chennai, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rakesh","family":"Bhatia","sequence":"additional","affiliation":[{"name":"Sarojini Naidu Medical College, Agra, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dipti","family":"Agarwal","sequence":"additional","affiliation":[{"name":"Sarojini Naidu Medical College, Agra, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Santosh","family":"Kumar","sequence":"additional","affiliation":[{"name":"Sarojini Naidu Medical College, Agra, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajeshwar","family":"Dayal","sequence":"additional","affiliation":[{"name":"Sarojini Naidu Medical College, Agra, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheo Pratap","family":"Singh","sequence":"additional","affiliation":[{"name":"Sarojini Naidu Medical College, Agra, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geetha","family":"Ramachandran","sequence":"additional","affiliation":[{"name":"National Institute for Research in Tuberculosis (ICMR), Chennai, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","volume-title":"Global TB report","author":"World Health Organization","year":"2017","unstructured":"World Health Organization. 2017. Global TB report. World Health Organization, Geneva, Switzerland. http:\/\/www.who.int\/tb\/publications\/global_report\/en\/."},{"key":"e_1_3_2_3_2","volume-title":"RNTCP guidelines for programmatic management of drug resistant tuberculosis (PMDT) in India","author":"Revised National TB Control Programme","year":"2012","unstructured":"Revised National TB Control Programme. 2012. RNTCP guidelines for programmatic management of drug resistant tuberculosis (PMDT) in India. 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