Hair-analysis for acetyl-isoniazid/isoniazid ratio and N-acetyl-transferase-2-genotype in patients on treatment for mycobacterium tuberculosis infection

Background: In the presence of non-compliance, drug malabsorption or widely spaced intermittent therapy genetically determined faster acetylation of isoniazid has been shown to lead to treatment failure and relapse. Hepatotoxicity and peripheral neuritis are associated with slow acetylation of isoniazid. Objectives were to investigate what determines hair-levels of isoniazid and to assess whether acetylator phenotype in form of the isoniazid/acetyl-isoniazid ratio in hair reflects N-acetyltransferase –2 (NAT-2) genotype. Patients and methods: Hair was obtained from patients on isoniazid treatment. Isoniazid and acetyl isoniazid levels in hair were determined using HPLC/MS. Isoniazid/Acetyl isoniazid ratios were correlated with genotype of the NAT-2 determined by PCR. Hair levels of isoniazid were related to age, gender, weight, body mass index (BMI) and ethnic group. Results: Hair levels of isoniazid and acetyl-isoniazid were measured in 40 patients and genotype determined in 24. Hair levels of isoniazid correlated significantly with age and weight (p<0.05), but not with BMI or ethnic group. Acetyl-isoniazid/isoniazid ratios were with a median of 15.2% (range 14.5 to 31.7, n=3) in homozygous rapid acetylator NAT-2 genotype and 37.3% (range 1.73 to 51.2, n=7) in the heterozygous rapid acetylator NAT-2 genotype both significantly higher than in the slow acetylator NAT-2 genotype with 5.8% (range 0.53 to 14.4, n=14). Conclusions: Results of hair-analysis for isoniazid showed age and weight dependency of isoniazid levels. Acetyl-isoniazid/isoniazid ratios were lower in patients with slow acetylator versus rapid acetylator genotypes.