Population screening for isoniazid acetylator phenotype.
OBJECTIVE
To establish a useful method for acetylator phenotypification and therapeutic drug monitoring of patients receiving isoniazid.


METHODS
Sixty patients with uncomplicated pulmonary tuberculosis were given a 5-mg/kg oral dose of isoniazid each. Plasma concentrations of isoniazid and its metabolite, acetyl-isoniazid, were determined by HPLC analyses at various post-dose times. From the isoniazid concentration and the concentration ratio of acetyl-isoniazid and isoniazid (metabolic ratio), phenotypification methods were assessed.


RESULTS
The metabolic ratios at 3 h post-dose revealed a trimodal distribution; a fast, intermediate and slow acetylator phenotype group. The 2-h and 6-h data showed different bimodal combinations of these phenotype groups. The metabolic ratio phenotypification method could be simplified by using the HPLC data directly without converting it to absolute concentrations.


CONCLUSIONS
A single-sample test based upon the plasma isoniazid concentration, combined with the metabolic ratio of acetyl-isoniazid and isoniazid, appears to be a reliable parameter for phenotype discrimination and for bioavailability testing.
Seifart
H I
HI
Department of Pharmacology, University of Stellenbosch, Republic of South Africa.
Parkin
D P
DP
Botha
F J
FJ
Donald
P R
PR
Van Der Walt
B J
BJ
D000107:Acetylation; D000328:Adult; D000995:Antitubercular Agents / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D019540:Area Under Curve; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D016903:Drug Monitoring; D005260:Female; D005838:Genotype; D006801:Humans; D007538:Isoniazid / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008297:Male; D010641:Phenotype; D011110:Polymorphism, Genetic; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy* / Q000378:metabolism
D000995:Antitubercular Agents; D007538:Isoniazid