Example: Isoniazid (INH) is a drug used in the prophylaxis from tuberculosis. INH is eliminated mainly through two major pathways including acetylation and renal elimination. Acetylator phenotype is an important factor in determining the rate of INH elimination. The average estimated CLT and CLR in rapid acetylators are 350 ml/min, and 50 ml/min and in slow acetylators are 150 ml/min and 50 ml/min. Discuss the differences in INH elimination in rapid and slow acetylators.
300 ml/min
50 ml/min
Renal excretion
100 ml/min
50 ml/min
Renal excretion
Rapid acetylators eliminate INH faster than slow acetylators
Larger fraction of INH dose is metabolized by acetylation in rapid acetylators
Metabolite elimination is not different in the two populations
Rapid acetylators
eliminate INH
faster than slow
acetylators
Rapid acetylators will
form more acetyl
metabolite than slow
acetylators
The elimination rate
of INH metabolite is
not dependent on the
acetylator phenotype
The metabolite AUC
is larger in rapid
acetvlators due to the
formation of larger amount
of the acetyl metabolite
Rapid acetylators eliminate INH faster than slow acetylators
This is because the metabolic clearance and the CLT of INH are larger in rapid acetylators.
Rapid acetylators form more acetyl metabolite than slow acetylators.
This is because the metabolic clearance of INH represent a larger fraction of the CLT in rapid acetylators.
The metabolite AUC is larger in rapid acetylators compared to slow acetylators
This is because larger amount of the metabolite is formed in rapid acetylators and the metabolite elimination is not different in the two populations.
