TY - JOUR
T1 - Suboptimal Antituberculosis Drug Concentrations and Outcomes in Small and HIV-Coinfected Children in India
T2 - Recommendations for Dose Modifications
AU - Guiastrennec, Benjamin
AU - Ramachandran, Geetha
AU - Karlsson, Mats O.
AU - Kumar, A. K.Hemanth
AU - Bhavani, Perumal Kannabiran
AU - Gangadevi, N. Poorana
AU - Swaminathan, Soumya
AU - Gupta, Amita
AU - Dooley, Kelly E.
AU - Savic, Radojka M.
N1 - Publisher Copyright:
© 2017 The Authors Clinical Pharmacology & Therapeutics published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics
PY - 2018/10
Y1 - 2018/10
N2 - This work aimed to evaluate the once-daily antituberculosis treatment as recommended by the new Indian pediatric guidelines. Isoniazid, rifampin, and pyrazinamide concentration–time profiles and treatment outcome were obtained from 161 Indian children with drug-sensitive tuberculosis undergoing thrice-weekly dosing as per previous Indian pediatric guidelines. The exposure–response relationships were established using a population pharmacokinetic-pharmacodynamic approach. Rifampin exposure was identified as the unique predictor of treatment outcome. Consequently, children with low body weight (4–7 kg) and/or HIV infection, who displayed the lowest rifampin exposure, were associated with the highest probability of unfavorable treatment (therapy failure, death) outcome (Punfavorable). Model-based simulation of optimized (Punfavorable ≤ 5%) rifampin once-daily doses were suggested per treatment weight band and HIV coinfection status (33% and 190% dose increase, respectively, from the new Indian guidelines). The established dose-exposure–response relationship could be pivotal in the development of future pediatric tuberculosis treatment guidelines.
AB - This work aimed to evaluate the once-daily antituberculosis treatment as recommended by the new Indian pediatric guidelines. Isoniazid, rifampin, and pyrazinamide concentration–time profiles and treatment outcome were obtained from 161 Indian children with drug-sensitive tuberculosis undergoing thrice-weekly dosing as per previous Indian pediatric guidelines. The exposure–response relationships were established using a population pharmacokinetic-pharmacodynamic approach. Rifampin exposure was identified as the unique predictor of treatment outcome. Consequently, children with low body weight (4–7 kg) and/or HIV infection, who displayed the lowest rifampin exposure, were associated with the highest probability of unfavorable treatment (therapy failure, death) outcome (Punfavorable). Model-based simulation of optimized (Punfavorable ≤ 5%) rifampin once-daily doses were suggested per treatment weight band and HIV coinfection status (33% and 190% dose increase, respectively, from the new Indian guidelines). The established dose-exposure–response relationship could be pivotal in the development of future pediatric tuberculosis treatment guidelines.
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U2 - 10.1002/cpt.987
DO - 10.1002/cpt.987
M3 - Article
C2 - 29247506
AN - SCOPUS:85041337079
SN - 0009-9236
VL - 104
SP - 733
EP - 741
JO - Clinical pharmacology and therapeutics
JF - Clinical pharmacology and therapeutics
IS - 4
ER -