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Plasma levels of free and acid‐labile hydralazine: Effects of multiple dosing and of procainamide
Author(s) -
Schneck Dennis W.,
Sprouse Jeffrey S.,
Miller Kenneth,
Vary Jean E.,
DeWitt Floyd O.,
Hayes Arthur Hull
Publication year - 1978
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 - 10.1002/cpt1978246714
Subject(s) - procainamide , chemistry , metabolite , steady state (chemistry) , pharmacokinetics , endocrinology , hydralazine , medicine , dosing , plasma levels , pharmacology , dose–response relationship , blood pressure
The steady‐state plasma levels of unchanged free (H) and its ALC were measured in 6 normal volunteers—3 RA and 3 SA. All subjects received 25 mg H every 6 hr for a total of 12 doses; RA received an additional dose of 50 mg in a similar manner. Peak plasma levels offree H occurred at ½ to 1 hr following drug administration and declined with a t½ of 3.5 to 4.5 hr in both RA and SA. In contrast, ALC levels remained approximately constant over the 8‐hr sampling period. In the SA the mean steady‐state plasma concentration of ALC was 28% of the free H at the 25‐mg dose level. In the RA the percentages were 25 at the 25‐mg dose and 22 at the 50‐mg dose. These results indicate that under steady‐state conditions H is present predominantly in its free form. Administration of H (12 doses; 25 or 50 mg every 6 hr) with PA (every 3 or 4 hr) resulted in no alteration in the plasma levels of either H and its ALC or PA and its acetylated metabolite. This remained true when each phenotype was considered separately. The results from this portion of the study demonstrate that in normal subjects therapeutic plasma levels of neither PA nor H interfere with the acetylation of the other. Possible explanations for the lack of an interaction are presented.