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

Antimicrobial Agents and Chemotherapy
A K Hemanth KumarGeetha Ramachandran

Abstract

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 μg/ml versus 7.3 μg/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 μg/ml · h versus 9.4 μg/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 fro...Continue Reading

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Citations

Mar 13, 2019·Antimicrobial Agents and Chemotherapy·Wael A AlghamdiCharles A Peloquin
Nov 16, 2019·American Journal of Respiratory and Critical Care Medicine·Payam NahidBarbara Seaworth
May 9, 2019·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Mirjam GrogerMichael Ramharter
Dec 25, 2019·Antimicrobial Agents and Chemotherapy·Henrik Bjugård NybergPaolo Denti
Mar 30, 2019·Indian Journal of Pediatrics·Geetha Ramachandran
May 7, 2019·Journal of Chemotherapy·Tommaso MatucciElena Chiappini

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