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Polymorphic acetylation of hydralazine
Author(s) -
Timbrell John A,
Harland Steven J,
Facchini Vincenzo
Publication year - 1980
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.1980.173
Subject(s) - hydralazine , metabolite , acetylation , chemistry , urine , active metabolite , pharmacology , chromatography , medicine , blood pressure , biochemistry , gene
The acetylation of hydralazine has been studied in hypertensive patients undergoing maintenance therapy with the drug. The patients were acetylator phenotyped with sulfamethazine. Using gas‐liquid chromatography and high‐pressure liquid chromatography, hydralazine and two of its acetylated metabolites, methyltriazolophthalazine (MTP) and 3‐hydroxymethyltriazolophthalazine (HOMTP), have been determined in the 0‐ to 24‐hr urine. The excretion of hydralazine and HOMTP but not MTP was found to be related to the acetylator phenotype. The metabolic ratio HOMTP: hydralazine showed a bimodal distribution and the average ratio for slow acetylators (1.6) was lower than the ratio in rapid acetylators (14.9). It is concluded that hydralazine is polymorphically acetylated in man. The acetylated metabolite HOMTP was not, however, the major metabolite reported previously. Clinical Pharmacology and Therapeutics (1980) 28, 350–355; doi: 10.1038/clpt.1980.173