Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2016 Dec;7(6):239-247.
doi: 10.1177/2042098616667704. Epub 2016 Sep 7.

Rifampicin and isoniazid plasma concentrations in relation to adverse reactions in tuberculosis patients: a retrospective analysis

L Aït Moussa  1 , O El Bouazzi  2 , S Serragui  3 , D Soussi Tanani  4 , A Soulaymani  5 , R Soulaymani  6
Affiliations

Rifampicin and isoniazid plasma concentrations in relation to adverse reactions in tuberculosis patients: a retrospective analysis

L Aït Moussa et al. Ther Adv Drug Saf. 2016 Dec.

Abstract

Objective: High concentrations of antituberculosis (anti-TB) drugs can be associated with many adverse drug reactions (ADRs). The objective of this study was to examine the plasma concentrations of rifampicin (RMP) and isoniazid (INH) in patients with and without ADRs.

Methods: Concentration monitoring data of patients treated with anti-TB drugs were retrospectively analyzed from 2009 to 2011. RMP and INH plasma concentrations were measured 2 and 3 h after drug administration respectively using high-performance liquid chromatography.

Results: A total of 54 out of 120 patients have experienced ADRs to anti-TB drugs. The median concentrations [interquartile range (IQR)] obtained in patients with and without ADRs were 6.7 mg/l (3.7-9.9) and 5.6 mg/l (2.9-8.6) (p = 0.56) for RMP and 4.3 mg/l (2.3-5.3) and 3.1 mg/l (1.7-4.8) (p = 0.04) for INH, respectively. Related median doses (IQR) were 8.7 mg/kg (8.0-10.0) and 8.6 mg/kg (6.5-9.9) (p = 0.42) for RMP and 4.8 mg/kg (4.3-5.0) and 4.0 mg/kg (2.8-5) (p < 0.01) for INH, respectively. Concentrations above the expected range in patients with and without ADRs were not reached for RMP, but were 76% and 65% for INH, respectively. Correlation between concentrations and doses has not been established for RMP or INH. In addition, high INH concentrations showed no association with sex, age, liver injury or renal or diabetes.

Conclusions: High INH concentrations were common in patients with and without ADRs whereas RMP concentrations were low or within the normal range in most patients. Further studies are required to assess the association between high INH concentrations and the occurrence of ADRs.

Keywords: adverse drug reactions; drug concentrations; isoniazid; rifampicin.

PubMed Disclaimer

Conflict of interest statement

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Figure 1.
Figure 1.
Rifampicin plasma concentrations versus doses in patients with and without adverse drug reactions (ADRs): •, patients with ADRs; ∆, patients without ADRs. Thin lines represent the therapeutic range of rifampicin 2 h after drug administration.
Figure 2.
Figure 2.
Isoniazid plasma concentrations versus doses in patients with and without adverse drug reactions (ADRs): •, patients with ADRs; ∆, patients without ADRs. Thin lines represent therapeutic range of isoniazid 3 h after drug administration.
See this image and copyright information in PMC

References

    1. Aït Moussa L., Khassouani C., Hûe B., Jana M., Bégaud B., Soulaymani R. (2002a) Determination of the acetylator phenotype in Moroccan tuberculosis patients using isoniazid as metabolic probe. Int J Clin Pharmacol Ther 40: 548–553. - PubMed
    1. Aït Moussa L., Khassouani C., Soulaymani R., Jana M., Cassanas G., Alric R., et al. (2002b) Therapeutic isoniazid monitoring using a simple high-performance liquid chromatographic method with ultraviolet detection. J Chromatogr B 766: 181–187. - PubMed
    1. Aouam K., Chaabane A., Loussaïef C., Ben Romdhane F., Boughattas N., Chakroun M. (2007) Les effets indésirables des antituberculeux: épidémiologie, mécanismes et conduite à tenir. Med Mal Infect 37: 253–261. - PubMed
    1. Bakayoko A., Kamagaté M., Daix A., Koné Z., Kadiatou K., Dao Y., et al. (2015) Suivi thérapeutique et pharmacologique de l’isoniazide chez les patients suivis pour tuberculose pulmonaire à Abidjan. Rev Mal Respi 32: A21–A22.
    1. Ben Fredj N., Gam R., Kerkni E., Chaabane A., Chadly Z., Boughattas N., et al. (2016) Risk factors of isoniazid-induced hepatotoxicity in Tunisian tuberculosis patients. Pharm J 2016: 1–6. - PubMed

LinkOut - more resources