The effects of acute ethanol intake on isoniazid pharmacokinetics.
OBJECTIVE
To assess effects of acute ethanol intake on the pharmacokinetics of isoniazid in healthy male volunteers.


METHODS
Sixteen healthy male, drug-free subjects were studied. Each received in the fasting state, on two occasions separated by at least 1 week, isoniazid (200 mg orally). On one occasion (assigned randomly), subjects received ethanol 0.73 g/kg, 1 h before isoniazid, followed by 0.11 g/kg ethanol orally every hour thereafter for 7 h. Plasma isoniazid and acetylisoniazid concentrations were measured by means of high-performance liquid chromatography. Blood ethanol concentrations were measured hourly by breath analysis. Plasma concentrations of isoniazid and acetylisoniazid were analysed using TOPFIT software.


RESULTS
Peak concentrations of isoniazid were reached within 90 min, in both the ethanol-treated and control groups. The ethanol dosage regimen used resulted in peak blood ethanol concentrations between 78 mg/l and 103 mg/l. There was no significant difference in area under the curve, half-life of elimination or the ratio of acetylisoniazid to isoniazid (AcINH/INH) in the sample withdrawn 3 h after isoniazid dose. Acetylator phenotype for patients was the same in both phases, whether assessed by half-life of isoniazid or the AcINH/INH ratio at 3 h.


CONCLUSIONS
Acute ethanol intake at this dose is unlikely to affect results of acetylation studies in which isoniazid is used as a substrate, whether the half-life of isoniazid or the AcINH /INH ratio at 3 h is used to phenotype patients.
Dattani
R G
RG
Department of Pharmacology, Therapeutics and Toxicology, UWCM Academic Centre, Llandough Hospital, University of Wales College of Medicine, CF64 2XX, Cardiff, UK. rupendattani@hotmail.com
Harry
F
F
Hutchings
A D
AD
Routledge
P A
PA
D000107:Acetylation; D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000995:Antitubercular Agents / Q000493:pharmacokinetics*; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D004347:Drug Interactions; D000431:Ethanol / Q000097:blood / Q000494:pharmacology*; D006207:Half-Life; D006801:Humans; D007538:Isoniazid / Q000493:pharmacokinetics*; D008297:Male
D000995:Antitubercular Agents; D002492:Central Nervous System Depressants; D000431:Ethanol; D007538:Isoniazid