Isoniazid acetylation phenotypes in the Sudanese population: findings and implications

Monadil H. Ali, Alian A. Alrasheedy, Dan Kibuule, Mohamed Azmi Hassali, Brian Godman, Mohamed F. Abdelwahab, Raef Y. Abbadi

Research output: Contribution to journalArticle

Abstract

Background: Isoniazid (INH) is the mainstay antimicrobial in the treatment of tuberculosis (TB). It is acetlylated in the liver to acetyl-INH. However, there is variation in rate of acetylation of INH among TB patients (i.e. fast, intermediate or slow acetylators) which impacts on the treatment outcomes. Aim: The isoniazid acetylation phenotypes in the expatriate Sudanese population were determined to provide future guidance since TB is prevalent in Sudan. Methods: A community-based trial among Sudanese expatriates in Saudi Arabia was undertaken to identify INH-acetylation phenotypes. After overnight fasting, a single dose of 200 mg of INH was given to the volunteers. Three hours later, 5 ml of blood were drawn from each volunteer and prepared for High-Performance Liquid Chromatography (HPLC) analysis. The main outcomes were INH and Acetyl-INH concentrations in plasma and the subsequent Acetyl-INH/INH metabolic ratio (MR). Results: The findings suggest that slow acetylation is highly prevalent among the study participants (n = 43; 84.31%). Moreover, there was no statistically significant correlation between age and the MR (r = −0.18, P = 0.20). Further, there was no significant association between gender and the MR (P = 0.124). Similarly, no significant association was found between smoking habits and MR (P = 0.24). Conclusion: Isoniazid phenotyping suggests predominantly slow acetylation among the Sudanese in this sample. The study found no statistically significant associations between the MR and age or gender or smoking.

LanguageEnglish
Article number100120
Number of pages21
JournalJournal of Clinical Tuberculosis and Other Mycobacterial Diseases
Volume17
Early online date6 Sep 2019
DOIs
Publication statusE-pub ahead of print - 6 Sep 2019

Fingerprint

Isoniazid
Acetylation
Phenotype
Tuberculosis
Population
Volunteers
Smoking
Sudan
Saudi Arabia
Habits
Fasting
High Pressure Liquid Chromatography
Liver

Keywords

  • acetylation
  • fast acetylators
  • INH
  • isoniazid
  • slow acetylators
  • tuberculosis
  • Sudanese populations

Cite this

Ali, M. H., Alrasheedy, A. A., Kibuule, D., Hassali, M. A., Godman, B., Abdelwahab, M. F., & Abbadi, R. Y. (2019). Isoniazid acetylation phenotypes in the Sudanese population: findings and implications. 17, [100120]. https://doi.org/10.1016/j.jctube.2019.100120
Ali, Monadil H. ; Alrasheedy, Alian A. ; Kibuule, Dan ; Hassali, Mohamed Azmi ; Godman, Brian ; Abdelwahab, Mohamed F. ; Abbadi, Raef Y. / Isoniazid acetylation phenotypes in the Sudanese population : findings and implications. 2019 ; Vol. 17.
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abstract = "Background: Isoniazid (INH) is the mainstay antimicrobial in the treatment of tuberculosis (TB). It is acetlylated in the liver to acetyl-INH. However, there is variation in rate of acetylation of INH among TB patients (i.e. fast, intermediate or slow acetylators) which impacts on the treatment outcomes. Aim: The isoniazid acetylation phenotypes in the expatriate Sudanese population were determined to provide future guidance since TB is prevalent in Sudan. Methods: A community-based trial among Sudanese expatriates in Saudi Arabia was undertaken to identify INH-acetylation phenotypes. After overnight fasting, a single dose of 200 mg of INH was given to the volunteers. Three hours later, 5 ml of blood were drawn from each volunteer and prepared for High-Performance Liquid Chromatography (HPLC) analysis. The main outcomes were INH and Acetyl-INH concentrations in plasma and the subsequent Acetyl-INH/INH metabolic ratio (MR). Results: The findings suggest that slow acetylation is highly prevalent among the study participants (n = 43; 84.31{\%}). Moreover, there was no statistically significant correlation between age and the MR (r = −0.18, P = 0.20). Further, there was no significant association between gender and the MR (P = 0.124). Similarly, no significant association was found between smoking habits and MR (P = 0.24). Conclusion: Isoniazid phenotyping suggests predominantly slow acetylation among the Sudanese in this sample. The study found no statistically significant associations between the MR and age or gender or smoking.",
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Ali, MH, Alrasheedy, AA, Kibuule, D, Hassali, MA, Godman, B, Abdelwahab, MF & Abbadi, RY 2019, 'Isoniazid acetylation phenotypes in the Sudanese population: findings and implications' vol. 17, 100120. https://doi.org/10.1016/j.jctube.2019.100120

Isoniazid acetylation phenotypes in the Sudanese population : findings and implications. / Ali, Monadil H.; Alrasheedy, Alian A.; Kibuule, Dan; Hassali, Mohamed Azmi; Godman, Brian; Abdelwahab, Mohamed F.; Abbadi, Raef Y.

Vol. 17, 100120, 31.12.2019.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Isoniazid acetylation phenotypes in the Sudanese population

T2 - findings and implications

AU - Ali, Monadil H.

AU - Alrasheedy, Alian A.

AU - Kibuule, Dan

AU - Hassali, Mohamed Azmi

AU - Godman, Brian

AU - Abdelwahab, Mohamed F.

AU - Abbadi, Raef Y.

PY - 2019/9/6

Y1 - 2019/9/6

N2 - Background: Isoniazid (INH) is the mainstay antimicrobial in the treatment of tuberculosis (TB). It is acetlylated in the liver to acetyl-INH. However, there is variation in rate of acetylation of INH among TB patients (i.e. fast, intermediate or slow acetylators) which impacts on the treatment outcomes. Aim: The isoniazid acetylation phenotypes in the expatriate Sudanese population were determined to provide future guidance since TB is prevalent in Sudan. Methods: A community-based trial among Sudanese expatriates in Saudi Arabia was undertaken to identify INH-acetylation phenotypes. After overnight fasting, a single dose of 200 mg of INH was given to the volunteers. Three hours later, 5 ml of blood were drawn from each volunteer and prepared for High-Performance Liquid Chromatography (HPLC) analysis. The main outcomes were INH and Acetyl-INH concentrations in plasma and the subsequent Acetyl-INH/INH metabolic ratio (MR). Results: The findings suggest that slow acetylation is highly prevalent among the study participants (n = 43; 84.31%). Moreover, there was no statistically significant correlation between age and the MR (r = −0.18, P = 0.20). Further, there was no significant association between gender and the MR (P = 0.124). Similarly, no significant association was found between smoking habits and MR (P = 0.24). Conclusion: Isoniazid phenotyping suggests predominantly slow acetylation among the Sudanese in this sample. The study found no statistically significant associations between the MR and age or gender or smoking.

AB - Background: Isoniazid (INH) is the mainstay antimicrobial in the treatment of tuberculosis (TB). It is acetlylated in the liver to acetyl-INH. However, there is variation in rate of acetylation of INH among TB patients (i.e. fast, intermediate or slow acetylators) which impacts on the treatment outcomes. Aim: The isoniazid acetylation phenotypes in the expatriate Sudanese population were determined to provide future guidance since TB is prevalent in Sudan. Methods: A community-based trial among Sudanese expatriates in Saudi Arabia was undertaken to identify INH-acetylation phenotypes. After overnight fasting, a single dose of 200 mg of INH was given to the volunteers. Three hours later, 5 ml of blood were drawn from each volunteer and prepared for High-Performance Liquid Chromatography (HPLC) analysis. The main outcomes were INH and Acetyl-INH concentrations in plasma and the subsequent Acetyl-INH/INH metabolic ratio (MR). Results: The findings suggest that slow acetylation is highly prevalent among the study participants (n = 43; 84.31%). Moreover, there was no statistically significant correlation between age and the MR (r = −0.18, P = 0.20). Further, there was no significant association between gender and the MR (P = 0.124). Similarly, no significant association was found between smoking habits and MR (P = 0.24). Conclusion: Isoniazid phenotyping suggests predominantly slow acetylation among the Sudanese in this sample. The study found no statistically significant associations between the MR and age or gender or smoking.

KW - acetylation

KW - fast acetylators

KW - INH

KW - isoniazid

KW - slow acetylators

KW - tuberculosis

KW - Sudanese populations

UR - https://www.sciencedirect.com/journal/journal-of-clinical-tuberculosis-and-other-mycobacterial-diseases

U2 - 10.1016/j.jctube.2019.100120

DO - 10.1016/j.jctube.2019.100120

M3 - Article

VL - 17

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