Hair Analysis for Determination of Isoniazid Concentrations and Acetylator Phenotype during Antituberculous Treatment

Abstract

Background. Analysis of isoniazid (INH) uptake has been based on measurement of plasma concentrations providing a short-term and potentially biased view. Objectives. To establish hair analysis as a tool to measure long-term uptake of INH and to assess whether acetylator phenotype in hair reflects N-acetyltransferase-2 (NAT2) genotype. Design and Methods. INH and acetyl-INH concentrations in hair were determined in patients on INH treatment for M. tuberculosis infection using high pressure liquid chromatography/mass spectrometry. Acetyl-INH/INH ratios were correlated with NAT-2 genotype. Results. Hair concentrations of INH, determined in 40 patients, were not dependent on ethnic group or body mass index and were significantly higher in male compared to female patients (median (range) 2.37 ng/mg (0.76-4.9) versus 1.11 ng/mg (0.02-7.20) (P = 0.02). Acetyl-INH/INH ratios were a median of 15.2% (14.5 to 31.7) in homozygous rapid acetylator NAT-2 genotype and 37.3% (1.73 to 51.2) in the heterozygous rapid acetylator NAT-2 genotype and both significantly higher than in the slow acetylator NAT-2 genotype with 5.8% (0.53 to 14.4) (P < 0.05). Conclusions. Results of hair analysis for INH showed lower concentrations in females. Acetyl-INH/INH ratios were significantly lower in patients with slow acetylator versus rapid acetylator genotypes.

Figure 1

Isoniazid (INH) concentration in the hair shaft as function of distance from the scalp (cm) obtained 9 months after cessation of a 3-month course of treatment.

Figure 2

Isoniazid concentration in hair and gender.

Figure 3

Correlation of isoniazid concentration in hair and age.

Figure 4

Correlation of isoniazid concentrations and body weight (regression line inserted).

Figure 5

Acetylator phenotype represented as acetylisoniazid/isoniazid ratio (AcINH/INH ratio) and arylamine N-acetyltransferase 2 genotype (n = 24).