Evaluation of high through-to-peak ratio of perindopril in SHR.
The present study was designed to evaluate trough-to-peak ratio (T/P) of ACE inhibitors in spontaneously hypertensive rats (SHR) by a continuous monitoring of ambulatory blood pressure for 24 hours with a biotelemetric system. Blood pressure was recorded uninterruptedly with a battery-operated transmitter connected to a sensor catheter. Perindopril (3 mg/kg), trandolapril (1 mg/kg), quinapril (10 mg/kg) and enalapril (6 mg/kg) were given once a day for 7 days. On the first day of the treatment these ACE inhibitors equally decreased blood pressure by 20 mmHg at each peak. The peak and trough blood pressure decreased steadily until day 4, and then they were constant until the end of experiment (day 7). T/P for each inhibitor also increased until day 4, and the ratios in systolic blood pressure at the end of experiments (day 7) were as follows, perindopril: 0.63, trandolapril: 0.62, quinapril: 0.41, enalapril: 0.27. The T/P of perindopril was significantly higher than that of enalapril. The results of the present studies testing four ACE inhibitors are well consistent with those in clinical trials. Thus, the measurement of T/P in SHR would provide a meaningful information for the evaluation of antihypertensive agents like ACE inhibitors.
Moriyama
S
S
New Product Research Laboratories II, Tokyo R&D Center, Daiichi Pharmaceutical Co., Ltd., Japan.
Ishigai
Y
Y
Mori
T
T
Fukuzawa
A
A
Shibano
T
T
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D018660:Blood Pressure Monitoring, Ambulatory / Q000379:methods; D002940:Circadian Rhythm / Q000187:drug effects / Q000502:physiology*; D004656:Enalapril / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000188:drug therapy / Q000503:physiopathology*; D007211:Indoles / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology; D008124:Locomotion / Q000187:drug effects / Q000502:physiology*; D008297:Male; D020913:Perindopril / Q000494:pharmacology*; D000077583:Quinapril; D011897:Random Allocation; D051381:Rats; D011918:Rats, Inbred SHR; D013686:Telemetry; D044005:Tetrahydroisoquinolines
D000806:Angiotensin-Converting Enzyme Inhibitors; D007211:Indoles; D007546:Isoquinolines; D044005:Tetrahydroisoquinolines; C052035:trandolapril; D004656:Enalapril; D000077583:Quinapril; D020913:Perindopril