Acetylation of procaine amide in man studied with a new gas chromatographic method.

1 A specific gas-chromatographic method was developed for determination of N-acetylprocaine amide in plasma and urine, using 4-amino-N-(2-piperidinoethyl)benzamide as an internal standard. The investigation was performed in 50 cardiac patients who had reached steady-state plasma concentrations of procaine amide. 2 The plasma concentrations of the acetylated metabolite varied between 1.0 and 15.0 μg/ml and were thus of the same order of magnitude as those of the parent drug. Especially high plasma levels of the metabolite were seen in patients with poor kidney function. 3 The urinary excretion of the metabolite varied markedly between individuals and ranged between 6 and 52% of the administered daily dose. There was a clear tendency towards higher rates of acetylation of procaine amide in patients with short plasma half-lives of isoniazid, i.e. the phenotype rapid acetylators. Because of coexisting therapy with other drugs and impaired renal function in some patients studies are required in healthy human volunteers to ascertain whether the acetylation of procaine amide and isoniazid are mediated by the same enzyme system.