Pharmacokinetics of second-line anti-tuberculosis drugs in children with multidrug-resistant tuberculosis in India [PublishAheadOfPrint]

We studied the pharmacokinetics of levofloxacin (LFX), pyrazinamide (PZA), ethionamide (ETH) and cycloserine (CS) in children with multidrug-resistant tuberculosis (MDR TB) 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. Estimation of plasma LFX, PZA, ETH and CS were undertaken according to validated methods by HPLC. Adverse events were noted at six months of treatment. The peak concentration (C_max) of LFX was significantly higher in female than male children (11.5μg/ml vs 7.3μg/ml; p = 0.017). Children below 12 years had significantly higher exposure (AUC_0-8) of ETH than those above 12 years of age (17.5μg/ml.h vs 9.4μg/ml; p = 0.030). Multiple linear regression analysis showed significant influence of gender on C_{max of} ETH and age on C_max and AUC_0-8 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 programme. More studies on the safety and pharmacokinetics of second-line anti-TB drugs in children with MDR TB from different settings are required.

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