Comparative efficacy of high-dose versus low-dose nicorandil therapy for chronic stable angina pectoris

Kinoshita, Masahiko; Nishikawa, Shunsuke; Sawamura, Matsuhiko; Yamaguchi, Shinichiro; Mitsunami, Kenichi; Itoh, Makoto; Motomura, Masakazu; Bito, Keizo; Mashiro, Iwao; Kawakita, Seiichi

doi:10.1016/0002-9149(86)90347-4

Cited by 50 publications

(14 citation statements)

References 15 publications

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“…Figure 5 and Table 2 show the dose concentration curve after continuous infusion of nicorandil in eight dogs. At a dosage of 5 ~g/kg/min, which induced a clinically effective plasma level of nicorandil [21] of approximately 100 ng/ml, the dilatory action of nico- Table randil appeared in the large coronary arteries, but not in the coronary resistance vessels. At doses greater than 10 ~xg/kg/min, which induced plasma levels of nicorandil above 200 ng/ml, nicorandil had a significant effect, not only on epicardial coronary artery, but also on coronary resistance artery.…”

Section: Groupmentioning

confidence: 94%

Coronary effects of nicorandil in comparison with nitroglycerin in chronic conscious dogs

Hashimoto

Kinoshita

Ohbayashi

1991

Cardiovasc Drug Ther

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The effects of nicorandil (0.2 mg/kg, IV) and nitroglycerin (15 micrograms/kg, IV) on large and small coronary arteries were compared in conscious dogs instrumented with ultrasonic crystals and electromagnetic flow meters in the circumflex coronary artery. Nicorandil dilated the large coronary arteries to the same extent, but with a longer duration of action than nitroglycerin. The small coronary arteries dilated for a very short period of time with nitroglycerin, but dilated markedly with nicorandil. The dilatory action of nicorandil on large coronary arteries persisted after the action on the small coronary artery fell to the control value, indicating that the dilatory action on the large coronary arteries is due to the direct relaxing effect on smooth muscle and is not the result of the flow-dependent effect. The measurement of the plasma concentration of nicorandil after incremental infusions of the agent showed that the dilation of the small coronary artery took place at only a very high level (above 200 ng/ml). On the other hand, the large coronary arteries responded to nicorandil at a much lower concentration (about 100 ng/ml, the clinically effective plasma concentration of nicorandil) than the small coronary resistance arteries. In conclusion, whereas nicorandil possesses a dilatory action on both large and small coronary arteries, in a clinical setting, with a daily dosage of 15-30 mg, part of the beneficial effects of nicorandil may be the result of a dilation of the large coronary arteries and may be due to the fact that a coronary steal phenomenon does not occur after nicorandil administration.

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Section: Groupmentioning

confidence: 94%

Coronary effects of nicorandil in comparison with nitroglycerin in chronic conscious dogs

Hashimoto

Kinoshita

Ohbayashi

1991

Cardiovasc Drug Ther

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“…The increase of exercise duration following nicorandil was almost similar to that after nitroglycerin by 2.0 ___ 1.8 and 2.5 -1.7 minutes, respectively. The rate-pressure product at peak exercise was increased by nicorandil in Kinoshita's [92] as well as in Hayata's studies [117].…”

Section: Studies In Angina Pectarismentioning

confidence: 77%

“…When the effect of nicorandil was assessed in 11 patients with angina pectoris half an hour after single oral administration of 10 mg and 30 rag, however, exercise duration showed a significant positive correlation with the plasma drug concentration [92] and revealed that the therapeutic plasma levels required to increase exercise duration are approximately 100 ng/ ml [92].…”

Section: Plasma Drug Concentration and Clinical Effectsmentioning

confidence: 97%

“…The therapeutic efficacy of the drug can be evaluated by using a multistage exercise test [116]. Kinoshita et al [92] performed a comparative study on low-dose and high-dose nicorandil therapy in 11 patients with chronic stable angina pectoris. Ten milligrams of nicorandil increased exercise tolerance by 15%, while 30 mg increased it by 45%.…”

Section: Studies In Angina Pectarismentioning

confidence: 99%

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Pharmacology and therapeutic effects of nicorandil

Kinoshita

Sakai²

1990

Cardiovasc Drug Ther

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Nicorandil, a nicotinamide derivative, is an orally efficacious antianginal drug possessing a nitrate moiety in its chemical structure. This drug is an effective and well-tolerated treatment for various types of angina pectoris. Its general efficacy is similar to that of nitrates, with several unique effects on the cardiovascular system. Nicorandil causes sustained dilation of both the arterial resistance and conductive vessels, thus markedly dilating the coronary artery and increasing coronary blood flow. In addition, nicorandil, unlike nitroglycerin or isosorbide dinitrate, possesses little hemodynamic effect on heart rate, blood pressure, or cardiac contractility with clinical doses yielding antianginal effects. The mechanism causing coronary vasodilation has not been completely clarified but appears to be associated partly with increases in c-GMP, as well as the hyperpolarization of the smooth muscle membrane. Nicorandil, in single oral doses of 10-30 mg, has been shown to be effective in chronic stable angina, as assessed objectively by increases in exercise duration and/or the time to onset of ST-segment depression during treadmill exercise. In open studies and controlled efficacy evaluations, nicorandil in daily oral doses of 15-40 mg demonstrated significant effectiveness in the treatment of various types of angina pectoris. Headaches due to vasodilation may occur, and some side effects occurred in 5.1-34% of patients receiving nicorandil, but were generally minor in nature. There was no depressant effect on atrioventricular conduction, which occurs frequently in patients treated with calcium antagonists of the verapamil and diltiazem type. Nicorandil may be effective even in patients with rest and effort angina who do not respond to combination therapy with calcium antagonists and oral nitrates. Thus, nicorandil appears to be a valuable addition to the arsenal of antianginal drugs due to its low incidence of serious side effects.

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“…Nicorandil [N-(2-hydroxyethyl) nicotin amide nitrate (ester)] is a potent vasodilator without an effect on myocardial contractility and oxygen consumption, and is clinically used for the treatment of angina pectoris [9,16,19], It is said that the coronary vasodi lating action of nicorandil is related to its blood concentration, although interindivid ual variation exists [7], However, sufficient basic studies on the influence of various fac tors, especially of emotional stress, on nico randil plasma levels do not exist. The present authors already observed that nicorandil plasma levels were affected by physical stress such as foot shock [6], In the present paper, we report the influences of nonphysical (psy chological) stress as well as that of physical stress on nicorandil plasma levels in rats, using the communication box paradigm [14].…”

Section: Introductionmentioning

confidence: 99%

Influences of Psychological Stress Produced by Intraspecies Emotional Communication on Nicorandil Plasma Levels in Rats

et al. 1989

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Influences of emotional stress on nicorandil pharmacokinetics were studied in rats that received physical and psychological stimuli (referred to as ‘sender’ and ‘responder’ rats, respectively) using the communication box paradigm. Concerning pharmacokinetic, there was no marked difference in the T_max, K_a, K_el, T_½ and V_d between the sender rats and the nonstressed control rats when both of which were orally administered 10 mg/kg of nicorandil. But the C_max and AUC were lower and clearance (Cl) was higher in the sender rats. In the responder rats, there was no difference in T_max, K_a, K_el, and T_½. But the C_max and AUC were lower and the V_d was higher than those of the control rats. On the other hand, when nicorandil was administered in a dose of 5 mg/kg subcutaneously, T_max and T_½ in the sender rats did not differ from those of the controls, but the C_max, K_a and AUC were lower, and the K_el, V_d and Cl were higher. Between the responder and control rats, significant differences were found in all parameters except for V_d, i.e., C_max, K_a, T_½ and AUC were lower than those of control rats, and the T_max, K_el and Cl were higher than those of control rats. This indicates that pharmacokinetics of nicorandil when administered orally and subcutaneously were influenced not only by physical stress but also by psychological stress.

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Comparative efficacy of high-dose versus low-dose nicorandil therapy for chronic stable angina pectoris

Cited by 50 publications

References 15 publications

Coronary effects of nicorandil in comparison with nitroglycerin in chronic conscious dogs

Coronary effects of nicorandil in comparison with nitroglycerin in chronic conscious dogs

Pharmacology and therapeutic effects of nicorandil

Influences of Psychological Stress Produced by Intraspecies Emotional Communication on Nicorandil Plasma Levels in Rats

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