Effects of the new calcium antagonist efonidipine hydrochloride on resting and exercise hemodynamics in patients with stable effort angina.
The action of efonidipine hydrochloride ((+/-)-2-[benzyl(phenyl)-amino]ethyl 1,4-dihydro-2,6-dimethyl-5-(5,5-dimethyl-2-oxo-1, 3,2-dioxaphosphorinan-2-yl)-4-(3-nitrophenyl)-3-pyridinecarboxy late hydrochloride ethanol, CAS 1110011-76-8, NZ-105) a new dihydropyridine calcium antagonist, on cardiac hemodynamics at rest and during exercise as well as plasma concentration and pharmacokinetic parameters were studied in 9 patients with angina pectoris. NZ-105 was administered 40 mg once daily for a week and cardiac hemodynamics parameters were measured at rest and during exercise using a bicycle ergometer before and after treatment. All patients showed anginal symptoms during exercise before treatment, while only 4 showed anginal symptoms during exercise after treatment. Improvement on electrocardiograms (ECG) (> 0.1 treatment mV) was detected in 4 out of 9, and NZ-105 was recognized to have an anti-anginal action. The mean plasma concentration of NZ-105 at the time was 14.5 ng/ml. At rest, reduction in blood pressure and decrease in total peripheral vascular resistance were observed, however, NZ-105 showed no effect on heart rate, cardiac index, pulmonary arterial pressure and central venous pressure. During maximum exercise, a decrease in total peripheral vascular resistance, reduction in pulmonary arterial pressure and central venous pressure, increasing tendency of left ventricular ejection fraction, and increase in cardiac index were observed. However, NZ-105 showed no effect on heart rate and blood pressure. Based on the results mentioned above, cardiac hemodynamics of NZ-105 during exercise, featured primarily, reduction of afterload and improvement of cardiac functional deterioration due to exercise. In conclusion, NZ-105 is useful in patients with ischemic cardiac diseases by improving hemodynamics and ECG findings during exercise in patients with effort angina.
Saito
T
T
Third Department of Internal Medicine, School of Medicine, Chiba University, Japan.
Fujii
K
K
Takizawa
T
T
Toyosaki
T
T
Kuwabara
Y
Y
Kobayashi
S
S
Ichikawa
H
H
Karaki
A
A
Yamazaki
Y
Y
Iwata
J
J
Yamada
K
K
Tomiya
H
H
Takeda
K
K
Inagaki
Y
Y
D000787:Angina Pectoris / Q000503:physiopathology*; D019540:Area Under Curve; D002121:Calcium Channel Blockers / Q000097:blood / Q000494:pharmacology*; D002302:Cardiac Output / Q000187:drug effects; D002496:Central Venous Pressure / Q000187:drug effects; D004095:Dihydropyridines / Q000097:blood / Q000494:pharmacology*; D004562:Electrocardiography / Q000187:drug effects; D015444:Exercise / Q000502:physiology*; D005080:Exercise Test; D005260:Female; D006321:Heart / Q000000981:diagnostic imaging; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009596:Nitrophenols; D009943:Organophosphorus Compounds / Q000097:blood / Q000494:pharmacology*; D011877:Radionuclide Imaging; D012146:Rest / Q000502:physiology*; D013318:Stroke Volume / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D009596:Nitrophenols; D009943:Organophosphorus Compounds; C066425:efonidipine