Pharmacokinetics of second-line anti-tuberculosis drugs in children with multidrug-resistant tuberculosis in India.


Hemanth Kumar, A.K.; Kumar, A.; Kannan, T.; Bhatia, R.; Agarwal, D.; Kumar, S.; Dayal, R.; Singh, S.P.; Ramachandran, G.


Antimicrobial Agents and Chemotherapy; 2 018; 62(5): 1-9.


Abstract: We studied the pharmacokinetics of levo?oxacin (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 (C max ) of LFX was signi?cantly higher in female than male children (11.5 m g/ml versus 7.3 m g/ml; P = 0.017). Children below 12 years of age had signi?cantly higher ETH exposure (area under the concentration-time curve from 0 to 8 h [AUC 08 ]) than those above 12 years of age (17.5 m g/ml · h versus 9.4 m g/ml; P = 0.030). Multiple linear regression analysis showed signi?cant in?uence of gender on C max of ETH and age on C max and AUC 08 of CS. This is the ?rst 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.


Keywords: MDR-TB; Children; India; Pharmacokinetics



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