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Cardiovascular effects, pharmacokinetics, and converting enzyme inhibition of enalapril after morning versus evening administration
Author(s) -
Witte Klaus,
Weisser Karin,
Neubeck Monika,
Mutschler Ernst,
Lehmann Karla,
Hopf Rüdiger,
Lemmer Björn
Publication year - 1993
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.1993.129
Subject(s) - enalapril , evening , morning , pharmacokinetics , enalaprilat , blood pressure , medicine , ambulatory blood pressure , pharmacology , dosing , angiotensin converting enzyme , crossover study , lisinopril , clinical pharmacology , essential hypertension , enalapril maleate , endocrinology , placebo , physics , alternative medicine , pathology , astronomy
The cardiovascular effects and pharmacokinetics of once‐daily enalapril were studied after single‐dose and subchronic treatment in eight patients with hypertension by use of ambulatory blood pressure monitoring. Enalapril, 10 mg, was given at either 7 AM or 7 PM in a randomized crossover design. In addition, inhibition of serum converting enzyme was studied. Subchronic treatment at 7 am significantly reduced blood pressure during the day but was less effective at night. Subchronic dosing at 7 pm significantly further decreased nighttime blood pressure followed by a slow increase during the day, with no effect on elevated afternoon values. Peak concentrations of enalaprilat were found 3.5 hours (morning) and 5.6 hours (evening) after drug intake ( p < 0.05), whereas peak effects occurred 7.4 hours (morning) and 12 hours (evening) after drug administration. In conclusion, 24‐hour blood pressure profiles in patients with hypertension were significantly influenced by the time of enalapril dosing. Differences in effect profiles could not be attributed to similar changes in pharmacokinetics or to different time courses of angiotensin converting enzyme inhibition. Clinical Pharmacology and Therapeutics (1993) 54, 177–186; doi: 10.1038/clpt.1993.129