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Pharmacokinetics of isoniazid, rifampicin, pyrazinamide and ethambutol in HIV-infected Indian children.
Int J Tuberc Lung Dis 2016; 20(5):666-72IJ

Abstract

SETTING

Co-infection with the human immunodeficiency virus (HIV) may lead to inadequate plasma concentrations of anti-tuberculosis drugs in children with tuberculosis (TB).

OBJECTIVE

To describe the influence of HIV infection on the pharmacokinetics of isoniazid, rifampicin, pyrazinamide and ethambutol in children.

DESIGN

Prospective drug estimation study in two cohorts of children: HIV-infected (n = 24) and non-HIV-infected (n = 32) with TB. Dosages used were based on earlier World Health Organization recommendations. All four drugs were estimated simultaneously using liquid chromatography mass spectrometry.

RESULTS

The HIV-TB co-infected children had a mean age of 105.9 months (standard deviation 43.1); there were 10 girls (41.7%). The maximum plasma concentration (Cmax), time taken to achieve Cmax, area under curve from 0-4 h and 2 h concentrations of isoniazid (INH), rifampicin (RMP) and pyrazinamide (PZA) were not affected by the HIV status of the children. Ethambutol (EMB) concentrations were lower in HIV-TB co-infected children. Inadequate 2 h concentrations of INH, RMP and EMB were found in the majority of the children in both groups. PZA concentrations were adequate in almost all children. Younger age and lower dose were associated with lower 2 h concentrations of INH and RMP.

CONCLUSION

Inadequate concentrations of INH, RMP and EMB in both HIV-TB-infected and non-HIV-infected children provide support for the recently revised recommended doses of INH and RMP. EMB levels were lower in HIV-infected children; however, more studies are needed to validate this observation.

Authors+Show Affiliations

Department of Paediatrics, All India Institute of Medical Sciences, New Delhi, India.Department of Ocular Pharmacology, All India Institute of Medical Sciences, New Delhi, India.Department of Paediatrics, All India Institute of Medical Sciences, New Delhi, India.Department of Ocular Pharmacology, All India Institute of Medical Sciences, New Delhi, India.Department of Paediatrics, All India Institute of Medical Sciences, New Delhi, India.Department of Paediatrics, All India Institute of Medical Sciences, New Delhi, India.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

27084822

Citation

Mukherjee, A, et al. "Pharmacokinetics of Isoniazid, Rifampicin, Pyrazinamide and Ethambutol in HIV-infected Indian Children." The International Journal of Tuberculosis and Lung Disease : the Official Journal of the International Union Against Tuberculosis and Lung Disease, vol. 20, no. 5, 2016, pp. 666-72.
Mukherjee A, Velpandian T, Singla M, et al. Pharmacokinetics of isoniazid, rifampicin, pyrazinamide and ethambutol in HIV-infected Indian children. Int J Tuberc Lung Dis. 2016;20(5):666-72.
Mukherjee, A., Velpandian, T., Singla, M., Kanhiya, K., Kabra, S. K., & Lodha, R. (2016). Pharmacokinetics of isoniazid, rifampicin, pyrazinamide and ethambutol in HIV-infected Indian children. The International Journal of Tuberculosis and Lung Disease : the Official Journal of the International Union Against Tuberculosis and Lung Disease, 20(5), pp. 666-72. doi:10.5588/ijtld.15.0288.
Mukherjee A, et al. Pharmacokinetics of Isoniazid, Rifampicin, Pyrazinamide and Ethambutol in HIV-infected Indian Children. Int J Tuberc Lung Dis. 2016;20(5):666-72. PubMed PMID: 27084822.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Pharmacokinetics of isoniazid, rifampicin, pyrazinamide and ethambutol in HIV-infected Indian children. AU - Mukherjee,A, AU - Velpandian,T, AU - Singla,M, AU - Kanhiya,K, AU - Kabra,S K, AU - Lodha,R, PY - 2016/4/17/entrez PY - 2016/4/17/pubmed PY - 2017/1/18/medline SP - 666 EP - 72 JF - The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease JO - Int. J. Tuberc. Lung Dis. VL - 20 IS - 5 N2 - SETTING: Co-infection with the human immunodeficiency virus (HIV) may lead to inadequate plasma concentrations of anti-tuberculosis drugs in children with tuberculosis (TB). OBJECTIVE: To describe the influence of HIV infection on the pharmacokinetics of isoniazid, rifampicin, pyrazinamide and ethambutol in children. DESIGN: Prospective drug estimation study in two cohorts of children: HIV-infected (n = 24) and non-HIV-infected (n = 32) with TB. Dosages used were based on earlier World Health Organization recommendations. All four drugs were estimated simultaneously using liquid chromatography mass spectrometry. RESULTS: The HIV-TB co-infected children had a mean age of 105.9 months (standard deviation 43.1); there were 10 girls (41.7%). The maximum plasma concentration (Cmax), time taken to achieve Cmax, area under curve from 0-4 h and 2 h concentrations of isoniazid (INH), rifampicin (RMP) and pyrazinamide (PZA) were not affected by the HIV status of the children. Ethambutol (EMB) concentrations were lower in HIV-TB co-infected children. Inadequate 2 h concentrations of INH, RMP and EMB were found in the majority of the children in both groups. PZA concentrations were adequate in almost all children. Younger age and lower dose were associated with lower 2 h concentrations of INH and RMP. CONCLUSION: Inadequate concentrations of INH, RMP and EMB in both HIV-TB-infected and non-HIV-infected children provide support for the recently revised recommended doses of INH and RMP. EMB levels were lower in HIV-infected children; however, more studies are needed to validate this observation. SN - 1815-7920 UR - https://www.unboundmedicine.com/medline/citation/27084822/Pharmacokinetics_of_isoniazid_rifampicin_pyrazinamide_and_ethambutol_in_HIV_infected_Indian_children_ L2 - https://www.ingentaconnect.com/openurl?genre=article&issn=1027-3719&volume=20&issue=5&spage=666&aulast=Mukherjee DB - PRIME DP - Unbound Medicine ER -