ABSTRACT
The genetic variation in drug response has been recognized since the 1950s when some patients experienced prolonged neuromuscular blockade after receiving the muscle relaxant suxamethonium chloride in preparation for surgical procedures. These patients were found to have a less efcient genetic variant of the butylcholinesterase enzyme (atypical pseudocholinesterase) responsible for the hydrolysis of suxamethonium chloride. The reduced cholinesterase activity resulted in prolongation of the half-life of this muscle relaxant and slowed the recovery from surgical paralysis. Also, the genetic variation in the N-acetyltransferase enzyme divides patients to slow acetylators and rapid acetylators, who metabolize drugs through the acetylation pathway at two distinct rates. When these two patient populations receive the same dose of drugs that are metabolized through the acetylation pathway such as the antituberculosis drug isoniazid and the antiarrhythmic drug procainamide, higher steady-state drug concentration is achieved in the slow acetylator population.
