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Pharmacokinetics of repeated single oral doses of enalapril maleate (mk‐421) in normal volunteers
Author(s) -
Till Alice E.,
Gomez Hector J.,
Hichens Martin,
Bolognese James A.,
McNabb W. R.,
Brooks B. A.,
Noormohamed F.,
Lant A. F.
Publication year - 1984
Publication title -
biopharmaceutics and drug disposition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.419
H-Index - 58
eISSN - 1099-081X
pISSN - 0142-2782
DOI - 10.1002/bdd.2510050309
Subject(s) - enalaprilat , enalapril , enalapril maleate , pharmacokinetics , chemistry , urine , ace inhibitor , endocrinology , enzyme inhibitor , steady state (chemistry) , capsule , medicine , pharmacology , angiotensin converting enzyme , enzyme , biochemistry , blood pressure , biology , botany
Enalapril, the ethyl ester of a potent angiotensin converting enzyme inhibitor, enalaprilat, was administered to healthy volunteers as a capsule containing 10 mg of the maleate salt, every 24 h for eight doses. Serum profiles show little accumulation of enalaprilat following eight daily doses of enalapril maleate. An average effective half‐life for accumulation of approximately 11 h was calculated from urine data. Comparison of observed 24‐h urinary recoveries of enalaprilat to predicted steady‐state recovery indicates that an ‘average’ steady state for enalaprilat is attained by the third or fourth dose of enalapril maleate. Statistical comparison of daily urinary recoveries, as well as C min values for enalaprilat, confirm this. Observed fluctuations in serum and urine data during apparent steady state suggest some day‐to‐day variability in the absorption of enalapril maleate and/or its hydrolysis to enalaprilat. An accumulation ratio of 1·3 for enalaprilat was calculated from the predicted steady‐state urinary recovery and observed urinary recovery for dose one.