PMID- 29463539
OWN - NLM
STAT- In-Process
LR  - 20190311
IS  - 1098-6596 (Electronic)
IS  - 0066-4804 (Linking)
VI  - 62
IP  - 5
DP  - 2018 May
TI  - Pharmacokinetics of Second-Line Antituberculosis Drugs in Children with
      Multidrug-Resistant Tuberculosis in India.
LID - e02410-17 [pii]
LID - 10.1128/AAC.02410-17 [doi]
AB  - 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 (Cmax) of LFX was significantly higher in female than male children
      (11.5 mug/ml versus 7.3 mug/ml; P = 0.017). Children below 12 years of age had
      significantly higher ETH exposure (area under the concentration-time curve from 0
      to 8 h [AUC0-8]) than those above 12 years of age (17.5 mug/ml . h versus 9.4
      mug/ml; P = 0.030). Multiple linear regression analysis showed significant
      influence of gender on Cmax of ETH and age on Cmax and AUC0-8 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.
CI  - Copyright (c) 2018 American Society for Microbiology.
FAU - Hemanth Kumar, Agibothu Kupparam
AU  - Hemanth Kumar AK
AD  - National Institute for Research in Tuberculosis (ICMR), Chennai, India.
FAU - Kumar, Alok
AU  - Kumar A
AD  - Sarojini Naidu Medical College, Agra, India.
FAU - Kannan, Thiruvengadam
AU  - Kannan T
AD  - National Institute for Research in Tuberculosis (ICMR), Chennai, India.
FAU - Bhatia, Rakesh
AU  - Bhatia R
AD  - Sarojini Naidu Medical College, Agra, India.
FAU - Agarwal, Dipti
AU  - Agarwal D
AD  - Sarojini Naidu Medical College, Agra, India.
FAU - Kumar, Santosh
AU  - Kumar S
AD  - Sarojini Naidu Medical College, Agra, India.
FAU - Dayal, Rajeshwar
AU  - Dayal R
AD  - Sarojini Naidu Medical College, Agra, India.
FAU - Singh, Sheo Pratap
AU  - Singh SP
AD  - Sarojini Naidu Medical College, Agra, India.
FAU - Ramachandran, Geetha
AU  - Ramachandran G
AD  - National Institute for Research in Tuberculosis (ICMR), Chennai, India
      geetha202@rediffmail.com.
LA  - eng
PT  - Journal Article
DEP - 20180426
PL  - United States
TA  - Antimicrob Agents Chemother
JT  - Antimicrobial agents and chemotherapy
JID - 0315061
PMC - PMC5923136
OTO - NOTNLM
OT  - *India
OT  - *MDR-TB
OT  - *children
OT  - *pharmacokinetics
EDAT- 2018/02/22 06:00
MHDA- 2018/02/22 06:00
CRDT- 2018/02/22 06:00
PHST- 2017/11/23 00:00 [received]
PHST- 2018/02/08 00:00 [accepted]
PHST- 2018/02/22 06:00 [pubmed]
PHST- 2018/02/22 06:00 [medline]
PHST- 2018/02/22 06:00 [entrez]
AID - AAC.02410-17 [pii]
AID - 10.1128/AAC.02410-17 [doi]
PST - epublish
SO  - Antimicrob Agents Chemother. 2018 Apr 26;62(5). pii: AAC.02410-17. doi:
      10.1128/AAC.02410-17. Print 2018 May.