%0 Journal Article
%T Hair Analysis for Determination of Isoniazid Concentrations and Acetylator Phenotype during Antituberculous Treatment
%A Michael Eisenhut
%A Detlef Thieme
%A Dagmar Schmid
%A Sybille Fieseler
%A Hans Sachs
%J Tuberculosis Research and Treatment
%D 2012
%I Hindawi Publishing Corporation
%R 10.1155/2012/327027
%X 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¨C4.9) versus 1.11£¿ng/mg (0.02¨C7.20) ( ). 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) ( ). 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. 1. Introduction The first application of hair analysis in monitoring of anti-infective treatment was the measurement of hair concentrations of indinavir, a protease inhibitor, in patients with HIV infection. Indinavir hair concentrations were significantly higher in responders compared to nonresponders [1]. Previous studies analysed antiepileptic drugs in segments of hair of patients on treatment for epilepsy and found that variability of hair drug concentrations, reflecting variable antiepileptic drug ingestion over time, was greater in epileptic patients with sudden unexplained death [2]. Hair analysis in patients on carbamazepine for treatment of epilepsy showed a significant linear relationship between the prescribed dose, hair concentration, and total plasma concentration [3]. Failure of tuberculosis treatment and relapse of tuberculosis, with selection of drug resistance mutations, have not been associated with low maximum concentrations of antituberculosis drugs such as isoniazid (INH). These conditions have been, however, associated with low areas under the concentration curve (AUC) in plasma, which is found in patients with intermittent noncompliance to treatment, widely spaced intermittent therapy, and chronically reduced
%U http://www.hindawi.com/journals/trt/2012/327027/