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Nilvadipine

A Review of its Pharmacodynamic and Pharmacokinetic Properties, Therapeutic Use in Hypertension and Potential in Cerebrovascular Disease and Angina

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An Erratum to this article was published on 01 August 1995

Summary

Synopsis

Nilvadipine, a calcium antagonist of the dihydropyridine class, selectively blocks calcium channels in vascular smooth muscle. Compared with nifedipine, the prototype of the dihydropyridines, nilvadipine has a longer duration of action. The antihypertensive efficacy of nilvadipine appears to be comparable with that of nicardipine and nitrendipine, enalapril and captopril and hydrochlorothiazide/triamterene, although further clinical experience is required to establish the claimed advantages nilvadipine may have over the other dihydropyridine derivatives currently used to treat hypertension. Preliminary studies suggest that nilvadipine may also be useful in the treatment of patients with stable exertional or variant angina.

Studies conducted in Japan indicate that nilvadipine improves symptoms resulting from cerebral infarction in some patients, but further comparative studies are required to confirm these results.

The tolerability of nilvadipine appears to be comparable with that of nicardipine and better than that of nifedipine with respect to flushes, oedema and liver function abnormalities.

As is typical of calcium antagonists, there is no evidence of tolerance to the antihypertensive effects of nilvadipine. The drug is equally effective in treating hypertension in elderly and younger patients and does not appear to adversely affect glucose or lipid metabolism. Thus, provided its apparently good tolerability is confirmed by wider clinical experience, it should be a suitable alternative to other calcium antagonists when used alone or in conjunction with other drugs for the majority of patients with mild to moderate hypertension.

Pharmacodynamic Properties

Nilvadipine is a dihydropyridine calcium antagonist that selectively inhibits calcium-induced contraction of smooth muscle and has a longer duration of inhibitory action than nifedipine and nicardipine. The antihypertensive effects of nilvadipine have been demonstrated in healthy volunteers and in patients with hypertension. Heart rate is increased after single dose oral administration to healthy volunteers but is minimally affected during treatment of patients with essential hypertension. In patients with coronary heart disease, the decrease in blood pressure is accompanied by a decrease in vascular resistance and pulmonary artery wedge pressure and an increase in cardiac output. Nilvadipine selectively relaxes cerebral, coronary and vertebral arteries in vitro and attenuated infarcts produced by occlusion of cerebral arteries when administered to rats in vivo prior to occlusion. In a rat model of stroke, oral nilvadipine prevented neurological deficits and death at dosages lower than those required to decrease blood pressure. A single oral dose of nilvadipine increased cerebral blood flow in the affected side in patients with chronic cerebral infarction.

Oral administration of nilvadipine 8mg for periods of 12 weeks to 3 years did not influence glucose metabolism in patients with non-insulin-dependent diabetes mellitus or serum levels of aldosterone, adrenaline (epinephrine), noradrenaline (norepinephrine) or vasopressin in patients with hypertension. Similarly, nilvadipine either did not alter or tended to decrease serum levels of total cholesterol and low density lipoprotein (LDL) cholesterol and increase those of high density lipoprotein (HDL) cholesterol in patients with hypertension.

Nilvadipine has shown some antiatherogenic activity on animal models; however, the clinical significance of these findings is not known.

Pharmacokinetic Properties

There is a linear relationship between mean maximum plasma concentration (Cmax) of nilvadipine or area under the plasma concentration-time curve (AUC) and oral doses between 2 and 12mg in healthy volunteers. After oral administration of single doses of 4 and 8mg to Caucasian volunteers, Cmax values were 2 and 3.03 μg/L, respectively, while in Japanese volunteers, Cmax was 3.48 μg/L after a single 4mg dose and 6.69 μg/L after a 6mg dose. Following administration of nilvadipine 3 to 8mg 12-hourly for up to 21 days there was an increase in Cmax, AUC and trough plasma concentration compared with values after a single dose. Trough plasma concentrations also increased after repeated once-daily administration of a slow-release preparation. Nilvadipine undergoes considerable first-pass metabolism and absolute bioavailability has been estimated to be between 14 and 19%.

Apparent volume of distribution of nilvadipine was 24 L/kg after a single dose and 40 L/kg after repeated administration. Protein binding (determined by equilibrium dialysis) was about 98%, mainly to albumin. Nilvadipine is biotrans-formed to inactive metabolites, and the main metabolite, formed by oxidation of the dihydropyridine ring and subsequent cleavage of the methyl ester, accounted for up to 68% of the dose recovered in urine after repeated administration.

Elimination half-life in healthy volunteers, determined in studies employing a relatively short sampling time (24 to 32 hours), ranged from 9.76 to 18.2 hours. The pharmacokinetic properties of nilvadipine were not significantly influenced by renal impairment or age. There was an inverse relationship between Cmax and plasma albumin and a positive relationship between plasma nilvadipine concentration and the reduction in hepatic excretory capacity in patients with cirrhosis. The AUC in such patients tended to be higher than that in healthy volunteers.

A positive correlation between plasma nilvadipine concentration and antihypertensive effect was reported in elderly and younger patients with hypertension treated with nilvadipine 4 to 30mg daily for up to 28 days.

Therapeutic Efficacy

Noncomparative trials conducted mainly in Japanese patients with essential hypertension have reported that nilvadipine administered at a dosage of usually 4 to 8mg daily in 2 divided doses decreased mean systolic and diastolic blood pressure by about 8 to 14%. Antihypertensive efficacy appeared to be similar when nilvadipine was administered twice or 3 times daily as a standard-release product or once daily in sustained-release form.

In comparisons with the other dihydropyridine calcium antagonists nifedipine, nicardipine and nitrendipine, or captopril or enalapril, nilvadipine produced a similar decrease in blood pressure. Based on the median 24-hour blood pressure profile, the duration of action of nilvadipine was longer than that of nitrendipine. There appears to be no association between patient age and blood pressure reduction, although pretreatment blood pressure and the decrease achieved with nilvadipine were positively correlated.

In patients with blood pressure not adequately controlled by metoprolol 100 to 120mg daily, the addition of nilvadipine decreased mean arterial blood pressure by ≥13mm Hg or to ≤149/89mm Hg in 73% of patients. Similarly, combined treatment with nilvadipine plus hydrochlorothiazide/triamterene decreased diastolic blood pressure to>-90mm Hg in 70 to 80.6% of patients unresponsive to either drug alone, while a combination of nilvadipine and enalapril reduced blood pressure to this level in 53 to 58% of patients unresponsive to monotherapy with either drug.

Studies in which nilvadipine was administered for periods of up to 3 years have revealed no evidence that tolerance develops to the antihypertensive effect of the drug. The level of blood pressure achieved after 2 weeks of treatment with nilvadipine was maintained for the duration of the studies. In one uncontrolled study, treatment with nilvadipine for 6 to 12 months improved the quality of life in elderly patients with essential hypertension.

The clinical efficacy of nilvadipine has also been studied in patients with neurological sequelae resulting from cerebral infarct that had occurred at least 1 month before starting treatment. Symptomatic improvement was rarely marked, but was regarded as moderate in 20 to 55.6% of patients. There were no significant differences in efficacy between nilvadipine 4mg and nicardipine 60mg daily and greater improvement was seen in subjective and psychological symptoms than in neurological symptoms and ability to perform daily activities. Further comparative studies are required to determine the usefulness of nilvadipine in this clinical situation where unequivocal evidence of efficacy is difficult to establish.

Results of preliminary studies in patients with stable angina pectoris indicated that nilvadipine 4mg 3 times daily tended to be more effective than a low dose of diltiazem (30mg 3 times daily) in improving exercise performance and less effective than nifedipine 30mg daily in improving anginal symptoms. However, there were no significant differences between nilvadipine and the comparators in other criteria of efficacy. Preliminary studies suggest that nilvadipine may also be useful for the treatment of variant angina.

Tolerability

The adverse effects associated with nilvadipine, as with other calcium antagonists, result from its vasodilator effects and most commonly include flushes, headache, tachycardia, oedema, dizziness, nausea and sleep disturbances. Such effects are usually of mild to moderate severity and occur early in the course of treatment. The overall incidence of adverse effects was similar with nilvadipine 8 to 16mg daily and nifedipine 30 to 60mg daily, although the incidence of flushes, oedema and increases in serum alanine aminotransferase levels and the withdrawal rate were significantly higher with nifedipine than nilvadipine. In other clinical trials the tolerability of nilvadipine was comparable to that of metoprolol, nitrendipine, nicardipine and hydrochlorothiazide/triamterene, although enalapril appeared to be better tolerated than nilvadipine. Withdrawal of nilvadipine treatment because of adverse effects was usually necessary in about 1 to 5% of patients. Because adverse effect data were obtainable from only a small number of comparative clinical trials, the tolerability of nilvadipine relative to that of other calcium antagonists remains unclear.

Dosage and Administration

Nilvadipine is available as a standard-release film-coated tablet in Japan and as a sustained-release formulation in Europe. The recommended dosage in the treatment of hypertension is 4 to 8mg daily administered once daily as a sustained-release formulation or in 2 divided doses as a standard-release preparation. Dosage should be determined individually and adjusted to a maximum of 16mg daily in patients whose blood pressure is not adequately controlled at the lower dosage.

In Japan, nilvadipine is used to treat patients with sequelae of cerebral infarction. In this clinical situation the recommended dosage is 2mg twice daily, which may be increased to 4mg twice daily if necessary.

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References

  1. Bkaily G, Molyvdas PA, Ousterhout J, et al. New dihydropyridine drug, nilvadipine blocks the calcium slow action potential in rat-cultured aortic smooth muscle cells. Eur J Pharmacol 1986; 124: 59–65

    PubMed  CAS  Google Scholar 

  2. Furuta T. Prolonged inhibitory effects of nilvadipine (FR34235) following washout in isolated rabbit aorta and mesenteric artery. J Cardiovasc Pharmacol 1988; 11: 134–8

    PubMed  CAS  Google Scholar 

  3. Jim KF, Matthews WD. Comparison of the calcium antagonistic activity of nifedipine and FR34235 in the canine saphenous vein. J Cardiovasc Pharmacol 1985; 7: 458–62

    PubMed  CAS  Google Scholar 

  4. Ohtsuka M, Ono T, Shibayama F. Nilvadipine. Cardiovasc Drug Rev 1988; 6: 97–115

    Google Scholar 

  5. Ohtsuka M, Ono T, Hiroi J, et al. Comparison of the cardiovascular effect of FR34235, a new dihydropyridine, with other calcium antagonists. J Cardiovasc Pharmacol 1983; 5: 1074–82

    PubMed  CAS  Google Scholar 

  6. Ohtsuka M, Koibuchi Y, Sakai S, et al. Effects of nilvadipine on the cardiovascular system in experimental animals. Arzneimittelforschung 1988; 38: 1605–18

    PubMed  CAS  Google Scholar 

  7. Matsuo M, Koibuchi Y, Tomoi M, et al. Binding of the new calcium entry blocker nilvadipine to rat aortic and guinea pig left ventricular membranes. Arzneimittelforschung 1989; 39: 576–9

    PubMed  CAS  Google Scholar 

  8. Borchard U. Calcium antagonists in comparison: view of the pharmacologist. J Cardiovasc Pharmacol 1994; 24 Suppl. 2: 85–91

    Google Scholar 

  9. Honerjager P, Seibel K. Pharmacodynamics of nilvadipine, a new dihydropyridine-type calcium antagonist. J Cardiovasc Pharmacol 1992; 20 Suppl 6: 15–21

    Google Scholar 

  10. Cheung WK, Sia LL, Woodward DL, et al. Importance of oral dosing rate on the hemodynamic and pharmacokinetic profile of nilvadipine. J Clin Pharmacol 1988; 28: 1000–7

    Google Scholar 

  11. Berger HH, Albert FW. Nilvadipine in hypertension with renal dysfunction. J Cardiovasc Pharmacol 1992; 20 Suppl. 6: 73–9

    Google Scholar 

  12. Lossnitzer K, Huber HJ, Kuchlbauer R. 24-hour blood pressure control after single daily doses of nilvadipine in patients with essential hypertension. J Cardiovasc Pharmacol 1992; 20 Suppl. 6: 35–42

    Google Scholar 

  13. Keck M. Comparison of the efficacy of nilvadipine and nitrendipine on circadian blood pressure. J Cardiovasc Pharmacol 1992; 20 Suppl. 6: 43–9

    Google Scholar 

  14. Fritschka E. Comparisons of once-daily nilvadipine with enalapril and diuretic in patients with essential hypertension. J Cardiovasc Pharmacol 1992; 20 Suppl. 6: S62–8 [Summary in 2 parts (Part B)]

    PubMed  Google Scholar 

  15. Pollack KP. Longterm treatment with the new calcium antagonist nilvadipine in hypertensive patients [in German]. Geriatrie Forschung 1992; 2: 49–59

    Google Scholar 

  16. Mikawa K, Maekawa N, Hasegawa M, et al. Effects of nilvadipine on the cardiovascular responses to tracheal intubation. J Clin Anesth 1992 Jul–Aug; 4: 292–6

    PubMed  CAS  Google Scholar 

  17. Takabatake T, Yamamoto Y, Nakamura S, et al. Effect of the calcium antagonist nilvadipine on haemodynamics at rest and during cold stimulation in essential hypertyension. Eur J Clin Pharmacol 1987; 33: 215–9

    PubMed  CAS  Google Scholar 

  18. Nakanishi T, Nishimura M, Kubota S. Effects of nilvadipine on 24-hour blood pressure in patients with essential hypertension: a new evaluation method. Curr Ther Res 1989 Dec; 46: 1096–105

    Google Scholar 

  19. Sato H, Ikenouchi H, Aoyagi T, et al. Acute hemodynamic effects of nilvadipine, a new calcium channel blocker, in patients with congestive heart failure. J Cardiovasc Pharmacol 1990 Feb; 15: 317–22

    PubMed  CAS  Google Scholar 

  20. Yokota M, Koide M, Miyahara T, et al. Effects of a new second generation calcium channel blocker, nilvadipine (FR34235), on exercise-induced hemodynamic changes in stable angina pectoris. J Am Coll Cardiol 1987; 10: 830–6

    PubMed  CAS  Google Scholar 

  21. Furuichi Y, Takakura S, Satoh H, et al. The effect of nilvadipine, a dihydropyridine type calcium channel blocker, on local cerebral blood flow in rats. Jpn J Pharmacol 1992 Apr; 58: 457–60

    PubMed  CAS  Google Scholar 

  22. Takakura S, Satoh Y, Satoh H, et al. Effects of nilvadipine on regional cerebral blood flow and skin blood flow in anesthetized cats. Arch Int Pharmacodyn Ther 1992 Sep–Oct; 319: 38–48

    PubMed  CAS  Google Scholar 

  23. Isozumi K, Izumi Y, Fukuuchi Y, et al. Effects of nilvadipine on cerebral circulation and metabolism in cats. Arzneimittelforschung 1990 Apr; 40 Suppl. I: 421–4

    PubMed  CAS  Google Scholar 

  24. Kawamura S, Shirasawa M, Fukasawa H, et al. Attenuated neuropathology by nilvadipine after middle cerebral artery occlusion in rats. Stroke 1991 Jan; 22: 51–5

    PubMed  CAS  Google Scholar 

  25. Takakura S, Susumu T, Satoh H, et al. Nilvadipine, a new calcium channel blocker, reduces ischemic brain injury in rats. Jpn J Pharmacol 1991 Aug; 56: 547–50

    PubMed  CAS  Google Scholar 

  26. Kobayashi S, Yamaguchi S, Okada K, et al. Effect of single oral administration of nilvadipine on cerebral blood flow in chronic cerebral infarction. Angiology 1992 Oct; 43: 801–9

    PubMed  CAS  Google Scholar 

  27. Urushiyama K. Effect of nilvadipine (FK 235) on regional cerebral blood flow and its therapeutic efficacy in patients with chronic cerebral infarction [in Japanese]. Yakuri to Chiryo 1991 Feb; 19: 623–31

    Google Scholar 

  28. Tagawa A, Ino K. Effects of nlvadipine (FK235) on cerebral blood flow [in Japanese]. Rinshou to Kenkyo 1991; 68: 611–8

    Google Scholar 

  29. Takabatake T. Renal function during antihypertensive therapy with a calcium antagonist, nilvadipine. Yakuri to Chiryo 1989; 17: 2155–60

    Google Scholar 

  30. Allison N, Stote R, Dubb J, et al. The effect of single oral doses of SK&F 102362 (nilvadipine) on renal function in healthy subjects. Smith Kline & French Laboratories (Philadephia) data on file. Report No. 8540557; Nov 1984

  31. Mutoh S, Nomoto A, Sekiguchi C, et al. Protective action of a calcium antagonist, nilvadipine, against aortic calcium deposition — a pathogenic factor in atherosclerosis. Atherosclerosis 1988; 73: 181–9

    PubMed  CAS  Google Scholar 

  32. Arakawa H, Mutoh S, Hirosumi J. Effect of nilvadipine on balloon catheterization-induced intimai thickening of the coronary artery in miniature pigs. J Cardiovasc Pharmacol 1992 Nov; 20: 731–4

    PubMed  CAS  Google Scholar 

  33. Koibuchi Y, Sakai S, Miura S, et al. Suppression of atherogenesis in cholesterol-fed rabbits treated with nilvadipine, a new vasoselective calcium entry blocker. Atherosclerosis 1989 Oct; 79: 147–55

    PubMed  CAS  Google Scholar 

  34. Nomoto A, Hirosumi J, Sekiguchi C, et al. Antiatherogenic activity of FR34235 (nilvadipine), a new potent calcium antagonist. Atherosclerosis 1987; 64: 255–61

    PubMed  CAS  Google Scholar 

  35. Hirayama S, Hand H, Honjo Y. Effects of nilvadipine (Nivadil Rm) on lipid metabolism and platelet aggregation [in Japanese]. Shinryo to Shinyaku 1991; 28: 1224–30

    Google Scholar 

  36. Yamada Y, Yokota M, Furumichi T, et al. Protective effects of calcium channel blockers on hydrogen peroxide induced increases in endothelial permeability. Cardiovasc Res 1990 Dec; 24: 993–7

    PubMed  CAS  Google Scholar 

  37. Ujike H, Nakatsu T, Tanaka K, et al. Clinical efficacy of nilvadipine against psychiatric symptoms appearing post-cerebral infarction: a multicenter study in psychiatry [in Japanese]. Geriatric Medicine 1994; 32: 727–38

    Google Scholar 

  38. Lee HC, Hardman JM, Lum BK. The effects of the calcium entry blockers, nilvadipine and nitrendipine, on endotoxin-induced disseminated intravascular coagulation. Life Sci 1989; 45: 877–83

    PubMed  CAS  Google Scholar 

  39. Bazán NG. Effects of ischaemia and electroconvulsive shock on free fatty acid pool in the brain. Biochim Biophys Acta 1970; 218: 1–10

    PubMed  Google Scholar 

  40. Siesjö BK. Cerebral circulation and metabolism. J Neurosurg 1984; 60: 883–908

    PubMed  Google Scholar 

  41. Takakura S, Sogabe K, Satoh H, et al. Nilvadipine as a neuroprotective calcium entry blocker in a rat model of global cerebral ischemia — a comparative study with nicardipine hydrochloride. Neurosci Lett 1992 Jul 20; 141: 199–202

    PubMed  CAS  Google Scholar 

  42. Kuwaki T, Satoh H, Ono T, et al. Nilvadipine attenuates ischemic degradation of gerbil brain cytoskeletal proteins. Stroke 1989 Jan; 20: 78–83

    PubMed  CAS  Google Scholar 

  43. Takakura S, Furuichi Y, Yamamoto T, et al. Effect of nilvadipine on the development of neurological deficits in stroke-prone spontaneously hypertensive rats. Stroke 1994 Mar; 25: 677–82

    PubMed  CAS  Google Scholar 

  44. Feuerstein GZ. Effect of nilvadipine on the development of neurological deficits in stroke-prone spontaneously hypertensive rats. Editorial comment. Stroke 1994 Mar; 25: 682–3

    Google Scholar 

  45. Imamura T, Matsunaga K, Yamasa T, et al. Long-term effects of calcium antagonist nilvadipine (Nivadil Rm) on hypertensive left-ventricular hypertrophy [in Japanese]. Shinyaku to Rinsho 1992 Jan; 41: 111–7

    Google Scholar 

  46. Minakawa T. Nilvadipine in left ventricular hypertrophy [in Japanese]. Therapeutic Research 1992; 13: 1371–6

    Google Scholar 

  47. Momomura S-I, Takabatake Y, Hayashi T, et al. A clinical study on the beneficial effects of nilvadipine on left ventricular hypertrophy in patients with hypertension [in Japanese]. Kokyu to Junkan 1994 Feb; 42: 153–9

    Google Scholar 

  48. Kitaoka H. Antihypetensive effect and effect on glucose tolerance of nilvadipine (Nivadil) in patients with essential hypertension associated with diabetes mellitus [in Japanese]. Horumon to Rinsho 1992; 40: 63–7

    Google Scholar 

  49. Yokoyama J et al. The influence of nilvadipine (Nivadil RM) administration on glycemic control, serum lipids, blood pressure in diabetes with hypertension [in Japanese]. Yakuri to Chiryo 1994 Jan; 22: 623–33

    Google Scholar 

  50. Kawai K, Suzuki S, Murayama Y, et al. Comparison of the effects of nilvadipine and captopril on glucose and lipid metabolism in NIDDM patients with hypertension. Diabetes Res Clin Pract 1992 May; 16: 137–43

    PubMed  CAS  Google Scholar 

  51. Abe Y, Kikuchi H, Matsui G, et al. Clinical studt of nilvadipine in diabetic patients complicated with hypertension [in Japanese]. Igaku Yakugaku 1986; 16: 1599–604

    Google Scholar 

  52. Horiuchi I, Kawamoto T, Okamoto M, et al. Antihypertensive efficacy, and effects on lipid metabolism of nilvadipine [in Japanese]. Geriatr Med 1986; 24: 1671–9

    Google Scholar 

  53. Yamamoto T. Antihypertensive effect of nilvadipine (Nivadil Rm) with a long term single dose in aged and middle-aged essential hypertensive patients and influence on serum lipids [in Japanese]. Shinryo to Shinyaku 1992; 29: 1201–13

    Google Scholar 

  54. Mizuno K, Hashimoto S, Yabe R, et al. Antihypertensive effect of a new calcium channel blocker, FK 235, in essential hypertension. Res Commun Chem Pathol Pharmacol 1986; 52: 3–15

    PubMed  CAS  Google Scholar 

  55. Takata Y, Yoshizumi T, Ito Y, et al. Elevated plasma nilvadipine concentration after single and chronic oral administration to patients with chronic liver disease. Eur J Clin Pharmacol 1992 May; 42: 475–9

    PubMed  CAS  Google Scholar 

  56. Cheung WK, Woodward DL, Shin. K, et al. Pharmacokinetics of nilvadipine after single oral doses in healthy volunteers. Int J Clin Pharmacol Res 1988; 5: 299–305

    Google Scholar 

  57. Terakawa M, Tokuma. Y, Shishido A, et al. Pharmacokinetics of nilvadipine in healthy volunteers. J Clin Pharmacol 1987; 27: 111–7

    PubMed  CAS  Google Scholar 

  58. Cheung WK, Sia LL, Hibberd M, et al. Pharmacokinetics of nilvadipine after multiple oral dosing to steady-state. Drug Dev Ind Pharm 1989; 15: 51–63

    CAS  Google Scholar 

  59. Terakawa M, Tokuma Y, Kuwahara N, et al. Multiple-dose pharmacokinetics of nilvadipine in healthy volunteers. J Clin Pharmacol 1988; 28: 350–5

    PubMed  CAS  Google Scholar 

  60. Mignot A, Lefebvre MA, Parsy P, et al. Steady state pharmacokinetics of nilvadipine slow release pellet formulation. Eur J Clin Pharmacol 1989; 36: A304

    Google Scholar 

  61. Weir MR, Vlachkis ND, DeQuattro V, et al. Evaluation of the clinical pharmacology of nilvadipine in patients with mild to moderate essential hypertension. J Clin Pharmacol 1990 May; 30: 425–37

    PubMed  CAS  Google Scholar 

  62. Ogihara T, Otsuka Y, Kumahara Y, et al. Pharmacokinetics and antihypertensive effects of a single dose of nilvadipine (FK235) in elderly hypertensive patients [in Japanese]. Geriatr Med 1986; 24: 1439–45

    Google Scholar 

  63. Terakawa M, Tokuma Y, Shishido A, et al. Effect of two different meals on bioavailability of nilvadipine in healthy volunteers. J Clin Pharmacol 1987; 27: 293–6

    PubMed  CAS  Google Scholar 

  64. Kusumoto M. Pharmacokinetic interaction of nilvadipine with cimetidine [in Japanese]. Yakuri to Chiryo 1992 Mar; 20: 879–85

    CAS  Google Scholar 

  65. von-Nieciecki A, Huber HJ, Stanislaus F. Pharmacokinetics of nilvadipine. J Cardiovasc Pharmacol 1992; 20 Suppl. 6: 22–9

    Google Scholar 

  66. Niwa T, Tokuma Y, Noguchi H. Plasma protein binding of nilvadipine, a new dihydropyridine calcium antagonist, in man and dog. Res Commun Chem Pathol Pharmacol 1987; 55: 75–87

    PubMed  CAS  Google Scholar 

  67. Tokuma Y, Terashita. S, Fijiwara T, et al. Urinary metabolites of nilvadipine in man. Yakabutsu Dota 1987; 2: 649–55

    Google Scholar 

  68. Kelly JG, O’Malley K. Clinical pharmacokinetics of calcium antagonists: an update. Clin Pharmacokinet 1992; 22: 416–33

    PubMed  CAS  Google Scholar 

  69. Ohkura T, Itoh A, Miyauchi J, et al. Pharmacokinetics of nilvadipine, a calcium channel blocking agent, in patients with imparied renal functions. Rinsho Iyaku 1986; 2: 1497–506

    Google Scholar 

  70. Iwamoto M, Ueda A, Otani T. Clinical effect of nilvadipine in the long-term treatment of patients with essential hypertension [in Japanese]. Yakuri to Chiryo 1993 May; 21: 1527–37

    Google Scholar 

  71. Kajiwara N. Effects of FK 235 on circadian variations in blood pressure in essential hypertension patients. Rinsho to Kenkyu 1985; 62: 3971–80

    Google Scholar 

  72. Takahashi T, Tsuda Y, Miyamoto Y, et al. Assessment of therapeutic effect of nilvadipine (Nivadil Rm) for essential hypertension associated with cerebrovascular disorders [in Japanese]. Shinyaku to Rinsho 1992 Apr; 41: 872–8

    Google Scholar 

  73. Yamamoto Y, Ohiwa K, Satoi H, et al. Blood pressure diurnal variation in cases with cerebrovascular disorders. Influence of nilvadipine upon diurnal changes in blood pressure [in Japanese]. Shinryo to Shinyaku 1992; 29: 755–63

    Google Scholar 

  74. Freytag F. Calcium-channel blocker and carbohydrate-metabolism. Influence on glucose tolerance and insulin secretion [in German]. Therapiewoche 1992 Dec; 42: 3118–23

    Google Scholar 

  75. Kaneko Y, Ikeda M, Ishii M. The clinical usefulness of FK 235 in the long term treatment of essential hypertension [in Japanese]. Ther Res 1986; 5: 1157–74

    Google Scholar 

  76. Shimamoto K, Shikano Y, Wakabayashi H. Clinical usefulness of nilvadipine (Nivadil Rm) in long-term treatment of essential hypertension: a multicenter co-operative study [in Japanese]. Yakuri to Chiryo 1993 Jul; 21: 2281–94

    Google Scholar 

  77. Faust G. One-year study of nilvadipine administered once a day. Efficacy and long-term tolerability in hypertensives [in German]. Fortschr Med 1993 Apr 20; 111: 188–92

    PubMed  CAS  Google Scholar 

  78. Ikeda M, Kaneko Y, Kuramochi M, et al. Clinical utility of nilvadipine (FK 235) in the treatment of essential hypertension — a multicentre, double-blind, comparative trial using nicardipine as a control [in Japanese]. Igaku Ayumi 1987; 140: 539–69

    Google Scholar 

  79. Yamamoto T. Comparison between nilvadipine and captopril, each given on long term single dosage basis to aged and middle-aged patients with essential hypertension, and on hypotensive effect and degree of reduced pressure stemming from each [in Japanese]. Shinryo to Shinyaku 1992; 29: 2435–45

    Google Scholar 

  80. Kuramoto K. Double-blind studies of calcium antagonists in the treatment of hypertension in Japan. J Cardiovasc Pharmacol 1989; 13 Suppl. 1: S29–35

    PubMed  Google Scholar 

  81. Oka M, Okada S, Nagata M, et al. Hypotensive effect of nilvadipine on diurnal blood pressure changes in patients with essential hypertension — comparison between elderly and young patients [in Japanese]. Shinryo to Shinyaku 1992; 29: 925–33

    Google Scholar 

  82. Elliot HL. α1-Adrenoceptor responsiveness: the influence of age. J Cardiovasc Pharmacol 1988; 12 Suppl. 8: 116–20

    Google Scholar 

  83. Imamura T, Koga H, Hara K, et al. Clinical effects of nilvadipine on essential hypertension in combination with β-blocking agent [in Japanese]. Rinsho Iyaku 1986; 2: 1517–24

    Google Scholar 

  84. Lederle RM, Lederle E. Combination of nilvadipine with a beta-blocker in essential hypertension [in German]. Munch Med Wochenschr 1992 Oct 30; 134: 711–5

    Google Scholar 

  85. Nakanishi T, Takahashi H, Yoshimura M. Efficacy of nipradilol plus a calcium antagonist in hypertensive patients resistant to monotherapy with a calcium antagonist. Curr Ther Res 1992 Jan; 51: 137–44

    Google Scholar 

  86. Ono K. Antihypertensive effect of a new calcium antagonist, nilvadipine in combination with metoprolol in essential hypertension [in Japanese]. Kiso-to-Rinsho 1986; 20: 5997–6005

    Google Scholar 

  87. Ogihara T, Mikami H, Otsuka A, et al. Effect of nilvadipine on quality of life in patients with essential hypertension. Curr Ther Res 1992 Jan; 51: 154–62

    Google Scholar 

  88. Ogihara T, Ishikawa H, Mikami H, et al. Effect of alacepril on quality of life in the treatment of hypertension. Curr Ther Res 1991; 49: 862–9

    Google Scholar 

  89. Ohtomo E, Tohgi H, Hirai S, et al. Clinical efficacy of nilvadipine (FK235) on chronic cerebrovascular disorder: early phase II multicenter open study [in Japanese]. Rinsho Iyaku 1990; 6: 2573–91

    Google Scholar 

  90. Araga S, Sato T, Tabuchi Y, et al. Long-term clinical study of nilvadipine (FK235) in chronic cerebrovascular diseases [in Japanese]. Geriatr Med 1991; 29: 337–48

    Google Scholar 

  91. Kawamura M, Hirayama K, Nakajima M, et al. Experiences in the treatment of sequalae of cerebral infarction with nilvadipine [in Japanese]. Geriatr Med 1991; 29: 763–71

    Google Scholar 

  92. Matsunaga M, Narita S, Nagata K, et al. Assessment of clinical utility of nilvadipine in sequels after cerebral infarction [in Japanese]. Shinryo to Shinyaku 1992; 29: 425–36

    Google Scholar 

  93. Sako K. Clinical efficacy of nilvadipine (FK 235) on cerebral infarction [in Japanese]. Yakuri to Chiryo 1991 Feb; 19: 611–21

    Google Scholar 

  94. Sakuta M, Sugita K, Suzuki Y, et al. Clinical study of nilvadipine in patients with sequalae of cerebral infarction [in Japanese]. Geriatr Med 1992; 30: 351–68

    Google Scholar 

  95. Takada A, Kuratsu J, Nagahiro S, et al. Clinical investigation of nilvadipine in hypertensive patients with cerebrovascular complications [in Japanese]. Geriatr Med 1993; 31: 1253–63

    Google Scholar 

  96. Ohtomo E, Tohgi H, Kogure K, et al. Clinical evaluation of nilvadipine (FK235) on chronic cerebrovascular disorder — late phase II multicenter dose-finding double blind group comparative study [in Japanese]. Rinsho Iyaku 1991; 7: 103–27

    Google Scholar 

  97. Ohtomo E, Tohgi H, Kogure K, et al. Clinical efficacy of nilvadipine (FK235) on cerebral infarction: multicenter double blind group comparative study of nicardipine hydrochloride [in Japanese]. Rinsho Iyaku 1991; 7: 389–412

    Google Scholar 

  98. Kato K, Takahashi N, Iimura O, et al. Clinical effect of nilvadipine on angina pectoris: a multi-center double blind comparative study between 8mg b.i.d. and 4 mg t.i.d [in Japanese]. Rinsho Iyaku 1994; 10: 199–215

    Google Scholar 

  99. Kato K, Takahashi N, Murayama M, et al. Comparison of the antianginal effects of nilvadipine (FK 235) and diltiazem in patients with exertional angina [in Japanese]. Rinsho Iyaku 1987; 3: 105–32

    Google Scholar 

  100. Nakamura Y, Miyashita H, Iimura O, et al. A group comparative double-blind trial of nilvadipine with nifedipine in the treatment of angina pectoris in a multicenter cooperation [in Japanese]. Rinsho Iyaku 1986; 86: 1657–76

    Google Scholar 

  101. Kishida H, Toyama S, Yanaga T, et al. Effect of a new calcium antagonist, nilvadipine, on variant angina ppectoris evaluated by 24-hour holter electrocardiography. Jpn Heart J 1988; 29: 781–93

    PubMed  CAS  Google Scholar 

  102. Yamamoto T, Yajima H, Nakamura R. Antihypertensive effect of nilvadipine (Nivadil Rm tablets) and sustained nifedipine preparation (Adalat Rm tablets) viewed from diurnal changes in blood pressure [in Japanese]. Shinryo to Shinyaku 1992; 29: 1707–14

    Google Scholar 

  103. Ikeda M, Kaneko T, Ishii T, et al. An investigation of the utility of FK 235 in treatment of essential hypertension — monotherapy and concurrent diuretic therapy in a multicentre, open trial [in Japanese]. Rinsho to Kenkyu 1986; 63: 2017–30

    Google Scholar 

  104. Faust G. The tolerability of nilvadipine compared to nifedipine in patients with essential hypertension. J Cardiovasc Pharmacol 1992; 20 Suppl. 6: 56–61

    Google Scholar 

  105. Vollmuth M, Schmitt W. Effect of nilvadipine on nifedipine-induced ankle edema: results of a double-blind randomised comparative trial [in German]. Fortschr Med 1994; 18: 266–70

    Google Scholar 

  106. Hermans L, Deblander A, De Keyser P, et al. At eqipotent doses, isradipine is better tolerated than amlodipine in patients with mild-to-moderate hypertension: a double-blind, randomised parallel group trial. Br J Clin Pract 1994; 38: 335–40

    CAS  Google Scholar 

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  1. Adis International Limited, 41 Centorian Drive, Private Bag 65901, Mairangi Bay, Auckland, 10, New Zealand

    Rex N. Brogden & Donna McTavish

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An erratum to this article is available at http://dx.doi.org/10.1007/BF03258534.

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Brogden, R.N., McTavish, D. Nilvadipine. Drugs & Aging 6, 150–171 (1995). https://doi.org/10.2165/00002512-199506020-00007

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