Example: Procainamide (PA) is an antiarrhythmic drug eliminated by renal excretion and metabolism to the active metabolite N-acetylprocainamide (NAPA). The maximum NAPA conc achieved after a single iv dose of 300 mg PA is 0.45 mg/L. What is the maximum NAPA conc achieved after administration of a single iv dose of 600 mg PA, assuming that PA and NAPA disposition follows linear pharmacokinetics ?
Dose (mg)
Increasing the drug dose results
in a proportional increase in the
amount of the metabolite
formed since the fraction of the
drug dose converted to the
metabolite (fm) is constant.
Increasing PA dose from 300 mg to 600 mg results in the formation of twice as much NAPA.
The maximum NAPA conc will be 0.9 mg/L after administration of 600 mg PA. This is because the amount and the conc of NAPA will increase proportional to the increase in PA dose.
