Relative bioavailability of immediate‐ and sustained‐release hydralazine formulations

Thomas M. Ludden, K. S. Rotenberg, L. K. Ludden, Alexander M.M. Shepherd, J. R. Woodworth

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

The in vivo performance of hydralazine sustained‐release dosage forms prepared using an ethylcellulose‐coated drug:resin complex was studied in healthy males who were determined to be slow acetylators. Two studies were performed. The first study (I) compared four different coating levels (6.8, 8.7, 10, and 12%) with an immediate‐release tablet and a solution. The second study (II) compared three additional coating levels (4, 5, and 7.8%) to the 6.8% formulation from the first study. Both hydralazine peak blood concentration (Cmax) and area under the blood concentration‐time curves (AUC) decreased as the coating level increased [coating level (Cmax, ng/mL; AUC, ng h/mL): 4% (37; 58), 5% (31; 55), 6.8% (13; 42 and 14; 39); 7.8% (16; 38), 8.7% (11; 34), 10% (7.8; 21), 12% (8.9; 17)]. In Study I both the solution and the immediate‐release tablet were administered in two divided doses at 8 a.m. (fasting) and 2 p.m. (post‐prandial). There was evidence for decreased bioavailability of unchanged hydralazine after the 2 p.m. doses as compared with the 8 a.m. doses. On the other hand, an assay that measures primarily the pyruvic acid conjugate of hydralazine yielded much higher concentrations after the afternoon dose. The results of these studies indicate that a sustained‐release dosage form of hydralazine can be prepared using an ethyl‐cellulose coated drug:resin complex and its in vivo characteristics are related to the coating level. Hydralazine bioavailability is influenced by food or recent prior exposure to hydralazine.

Original languageEnglish (US)
Pages (from-to)1026-1032
Number of pages7
JournalJournal of Pharmaceutical Sciences
Volume77
Issue number12
DOIs
StatePublished - Dec 1988

ASJC Scopus subject areas

  • Pharmaceutical Science

Fingerprint Dive into the research topics of 'Relative bioavailability of immediate‐ and sustained‐release hydralazine formulations'. Together they form a unique fingerprint.

Cite this