86619
document
Chronopharmacology of enalapril in hypertensive patients . The pharmacokinetics and pharmacodynamics of enalapril , an angiotensin converting enzyme inhibitor , are reported to vary with the time of administration . The present study was undertaken to examine whether the effect of enalapril on plasma bradykinin ( BK ) , substance P and prostaglandin E2 ( PGE2 ) , which are likely to be involved in the mechanism of enalapril-induced cough , might also be affected by its time of administration . Enalapril 5 mg or placebo was given orally at 10:00 h ( day trial ) or 22:00 h ( night trial ) to 12 patients with essential hypertension . Serum concentrations of total drug ( enalapril + enalaprilat , its active metabolite ) during the day and night trials did not differ significantly at any time . However , serum enalaprilat tended to be higher and its maximum concentration greater in the day trial than in the night trial . Blood pressure 24 h after administration of enalapril was reduced at 22:00 h , but not at 10:00 h. Plasma BK tended to increase following enalapril administration at 10:00 h , but not at 22:00 h. Remarkable increases in plasma BK were observed in two patients in the day trial and one of them also complained of cough . However , no such increase in plasma BK or subsequent adverse effect were recorded in the night trial . Plasma substance P and PGE2 did not change significantly following enalapril administration either in the day or night trial . The results suggest that the response of BK to enalapril is affected by the time of administration . In patients who complain of cough during treatment with enalapril during the daytime , this adverse effect might be diminished or eliminated by a switch to night-time administration .
86620
Intervention_Pharmacological
enalapril
86621
Intervention_Pharmacological
enalapril
86622
Intervention_Pharmacological
enalapril
86623
Intervention_Pharmacological
Enalapril
86624
Intervention_Control
placebo
86625
Intervention_Pharmacological
enalapril
86626
Intervention_Control
enalaprilat
86627
Intervention_Pharmacological
serum enalaprilat
86628
Intervention_Pharmacological
enalapril
86629
Intervention_Pharmacological
enalapril
86630
Intervention_Pharmacological
enalapril
86631
Intervention_Pharmacological
enalapril
86632
Intervention_Pharmacological
enalapril
86633
Outcome_Physical
plasma bradykinin ( BK ) , substance P and prostaglandin E2 ( PGE2 )
86634
Outcome_Other
Serum concentrations of total drug ( enalapril + enalaprilat , its active metabolite )
86635
Outcome_Physical
serum enalaprilat
86636
Outcome_Physical
Blood pressure 24 h
86637
Outcome_Physical
Plasma BK
86638
Outcome_Physical
plasma BK
86639
Outcome_Physical
plasma BK
86640
Outcome_Adverse-effects
adverse effect
86641
Outcome_Physical
Plasma substance P
86642
Outcome_Physical
PGE2
86643
Outcome_Physical
cough
86644
Participant_Condition
hypertensive patients .
86645
Participant_Condition
12 patients with essential hypertension .