Inhibition of the metabolism of paracetamol by isoniazid.
1. The effect of isoniazid given daily for 7 days on paracetamol (acetaminophen) kinetics and metabolism was studied in 10 healthy volunteers. Paracetamol, 500 mg, was given before isoniazid, on day 7 of isoniazid administration, and 2 days after the last dose of isoniazid. 2. On day 7, isoniazid markedly inhibited the formation clearance of the glutathione and catechol metabolites by 69.7% and 62.2%, respectively. Total paracetamol clearance was lowered by 15.2%. There was no effect of isoniazid on the non-oxidative pathways of paracetamol elimination. 3. Two days after isoniazid was discontinued, paracetamol metabolism had returned to pre-isoniazid values.
Epstein
M M
MM
Department of Pharmacology & Therapeutics, University of Bristish Columbia, Vancouver, Canada.
Nelson
S D
SD
Slattery
J T
JT
Kalhorn
T F
TF
Wall
R A
RA
Wright
J M
JM
D000082:Acetaminophen / Q000097:blood / Q000378:metabolism*; D000107:Acetylation; D000328:Adult; D002396:Catechols / Q000378:metabolism; D005260:Female; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D007538:Isoniazid / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction; D010641:Phenotype
D002396:Catechols; D000082:Acetaminophen; D005978:Glutathione; D007538:Isoniazid