Frågedatum: 1992-06-25
RELIS database 1992; id.nr. 9194, DRUGLINE
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Importance of acetylator phenotype for procainamide dosage.



Fråga: Importance of acetylator phenotype for procainamide dosage.

Sammanfattning: The levels of procainamide and its active metabolite N-acetylprocainamide are dependent on acetylator phenotype, but other factors such as kidney function and cardiac disease are also important. The risk of developing SLE seems to be dependent on the exposure to procainamide rather than N-acetylprocainamide and is higher in slow acetylators. In general, determination of procainamide and N-acetylprocainamide in plasma is a better tool to optimize therapeutic effect and minimize toxic effects of procainamide.

Svar: About 50 percent of procainamide is eliminated unchanged by the kidneys. N-acetylprocainamide (NAPA) is a main active metabolite that is approximately equipotent with procainamide. The acetylation of procainamide is under the same monogenic control as e.g. isoniazide. Acetylprocainamide is also eliminated via the kidneys, and in renal insufficiency the accumulation of N-acetylprocainamide is even more pronounced than that of procainamide (1-3).

The incidence of development of antinuclear antibodies and systemic lupus erythematosus during procainamide treatment is considered to be related to the dosage, the duration of treatment and the acetylator phenotype. The amino group on the aromatic ring is suspected to be of importance (1) and acetylation of this amino group (NAPA) seems to block the lupus inducing effect (4). Most studies in which therapeutic drug monitoring of procainamide and NAPA have not been used, show increased risk for development of SLE-like syndrome in slow acetylators (1). Determination of acetylator phenotype may therefore be valuable.

However, the levels of procainamide and acetylprocainamide are also dependent on other factors, especially kidney but also cardiac function. Therapeutic drug monitoring of procainamide and NAPA is therefore to be recommended to optimize therapeutic effect and minimize concentration-dependent toxic effects (1,3).

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