Pharmacological, Pharmacokinetic, and Clinical Properties of Benidipine Hydrochloride, a Novel, Long-Acting Calcium Channel Blocker

Yao, Kozo; Nagashima, Ken; Miki, Hiroyuki

doi:10.1254/jphs.dtj05001x

Cited by 89 publications

(74 citation statements)

References 86 publications

(79 reference statements)

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“…The partition coefficient of benidipine has been reported to be 3.79 using the flask-shaking method. 36) In accordance with the product interview forms, the partition coefficient of PGF2α analogs are 4.3 for latanoprost, 4.5-4.6 for tafluprost, and 3< for travoprost (no description for bimatoprost). Moreover, they are partially distributed through the nasopharyngeal mucosa to the whole body without being metabolized by the hepatic enzyme, indicating the very high liposolubility.…”

Section: Discussionmentioning

confidence: 78%

“…This concept can clearly explain its strong and long-lasting activity and could apply to PGF2α analogs. It is said that this property seems to be associated with its high affinity for cell membranes, 36) and the water-to-octanol partition coefficient (log P ow ) is available as an index. The partition coefficient of benidipine has been reported to be 3.79 using the flask-shaking method.…”

Section: Discussionmentioning

confidence: 99%

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Blood Pressure Elevation Associated with Topical Prostaglandin F2α Analogs: An Analysis of the Different Spontaneous Adverse Event Report Databases

Ohyama

Kawakami

Inoue

2017

Biological & Pharmaceutical Bulletin

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Topical prostaglandin F2α (PGF2α) analogs are widely used as the first line of therapy for glaucoma. Systemic PGF2α is suggested to increase blood pressure. Some ophthalmic formulations with β-receptor blocking or α-receptor stimulating actions are reported to cause systemic adverse events such as a decrease in heart rate and blood pressure. The objective of this study was to evaluate the association between topical Key words prostaglandin F2α analog; blood pressure elevation; spontaneous reporting database; adverse event; reporting odds ratio Glaucoma is a progressive, chronic condition prevalent worldwide that causes damage to the optic nerve, resulting in irreversible visual impairment and blindness. Based on the status of the internal drainage system, this condition is divided into two major subtypes i.e., open angle and angle closure.1) Reducing intraocular pressure (IOP) is one of the best ways to prevent the development of glaucoma, although there is a kind of open angle glaucoma in which optic neuropathy occurs without IOP exceeding the normal range. The approximate number of glaucoma patients was 60.5 million in 2010 and is estimated to increase to 79.6 million by 2020.2)

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Section: Discussionmentioning

confidence: 78%

Section: Discussionmentioning

confidence: 99%

Blood Pressure Elevation Associated with Topical Prostaglandin F2α Analogs: An Analysis of the Different Spontaneous Adverse Event Report Databases

Ohyama

Kawakami

Inoue

2017

Biological & Pharmaceutical Bulletin

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“…[1][2][3] Benidipine is a potent and long-acting dihydropyridine calciumchannel blocker (CCB), which inhibits not only L-type and N-type calcium channels but also T-type calcium channels, and regulates the constriction and dilation of renal efferent arterioles. 5 The Combination Therapy of Hypertension to Prevent Cardiovascular Events (COPE) trial is a prospective, randomized, open-label, blinded-endpoint (PROBE) study to determine the optimal combination of CCB benidipine-based therapy for hypertension, 6,7 and the main results have demonstrated that the percentage of subjects achieving the target BP and the incidence of primary composite cardiovascular end points were similar among benidipine-thiazide diuretic (thiazide), benidipine-angiotensin-receptor blocker (ARB) and benidipine-b-blocker subgroups. However, second analyses suggested that benidipine combined with a b-blocker appeared to be less beneficial in reducing the risk of stroke compared with the benidipine-thiazide combination, and was associated with an increased incidence of new-onset diabetes compared with the benidipine-ARB combination.…”

Section: Introductionmentioning

confidence: 99%

Combination therapy for hypertension in the elderly: a sub-analysis of the Combination Therapy of Hypertension to Prevent Cardiovascular Events (COPE) Trial

et al. 2012

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The Combination Therapy of Hypertension to Prevent Cardiovascular Events (COPE) trial demonstrated that the calcium-channel blocker benidipine-based combination therapies with an angiotensin-receptor blocker (ARB), a b-blocker, or a thiazide diuretic (thiazide) were similarly effective in preventing cardiovascular events and achieving the target blood pressure (BP; o140/ 90 mm Hg). We further evaluated the efficacy and safety of these combination therapies in older (X65 years) and younger (o65 years) hypertensive patients. In this sub-analysis of the COPE trial 3293 patients (1533X65 years old and 1760 o65 years old) were randomly assigned to receive benidipine-based therapy with an ARB, a b-blocker or a thiazide. In each group, the average BP did not differ among the three treatment groups. The incidence of the primary cardiovascular composite end point in the older group was higher than in the younger group (12.7 vs. 8.3 per 1000 person-years, P¼0.023). The primary composite cardiovascular end point, achievement (%) of target BP, and cardiovascular hard composite end points were similar among the three treatment groups. However, the hazard ratios and 95% confidence intervals in older patients were 2.74 (1.08-6.96; b-blocker vs. thiazide, P¼0.022) for fatal and non-fatal stroke, and 2.47 (1.03-5.91; b-blocker vs. ARB, P¼0.043) for newonset diabetes. Thus, benidipine combined with an ARB, a b-blocker, or a thiazide was similarly effective in preventing cardiovascular events and achieving the target BP in both older and younger hypertensive patients. Further studies will be necessary to evaluate the usefulness of benidipine combined with a b-blocker in terms of the incidence of stroke and new-onset diabetes in older patients.

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“…Mibefradil selectively blocks T-type calcium channels and has been demonstrated to exert a cardioprotective effect in rats with acute myocardial infarction (28). Benidipine has been widely used for hypertension therapy as it is able to block the L-type and T-type calcium channels in various cell types (29).…”

Section: Discussionmentioning

confidence: 99%

Protection of the cochlear hair cells in adult C57BL/6J mice by T-type calcium channel blockers

Yu¹,

Wang²,

Xiao³

et al. 2016

Experimental and Therapeutic Medicine

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Abstract. The aim of the present study was to investigate the protective effect of T-type calcium channel blockers against presbycusis, using a C57BL/6J mice model. The expression of three T-type calcium channel receptor subunits in the cochlea of 6-8-week-old C57BL/6J mice was evaluated using reverse transcription-quantitative polymerase chain reaction. The results confirmed that the three subunits were expressed in the cochlea. In addition, the capacity of T-type calcium channel blockers to protect the cochlear hair cells of 24-26-week-old C57BL/6J mice was investigated in mice treated with mibefradil, benidipine or saline for 4 weeks. Differences in hearing threshold were detected using auditory brainstem recording (ABR), while differences in amplitudes were measured using a distortion product otoacoustic emission (DPOAE) test. The ABR test results showed that the hearing threshold significantly decreased at 24 kHz in the mibefradil-treated and benidipine-treated groups compared with the saline-treated group. The DPOAE amplitudes in the mibefradil-treated group were increased compared with those in the saline-treated group at the F2 frequencies of 11.3 and 13.4 kHz. Furthermore, the DPOAE amplitudes in the benidipine-treated group were increased compared with those in the saline-treated group at an F2 frequency of 13.4 kHz. The loss of outer hair cells (OHCs) was not evident in the mibefradil-treated group; however, the stereocilia of the inner hair cells (IHCs) were disorganised and sparse. In summary, these results indicate that the administration of a T-type calcium channel blocker for four consecutive weeks may improve the hearing at 24 kHz of 24-26-week-old C57BL/6J mice. The function and morphology of the OHCs of the C57BL/6J mice were significantly altered by the administration of a T-type calcium channel blocker; however, the IHCs were unaffected.

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Pharmacological, Pharmacokinetic, and Clinical Properties of Benidipine Hydrochloride, a Novel, Long-Acting Calcium Channel Blocker

Cited by 89 publications

References 86 publications

Blood Pressure Elevation Associated with Topical Prostaglandin F2α Analogs: An Analysis of the Different Spontaneous Adverse Event Report Databases

Blood Pressure Elevation Associated with Topical Prostaglandin F2α Analogs: An Analysis of the Different Spontaneous Adverse Event Report Databases

Combination therapy for hypertension in the elderly: a sub-analysis of the Combination Therapy of Hypertension to Prevent Cardiovascular Events (COPE) Trial

Protection of the cochlear hair cells in adult C57BL/6J mice by T-type calcium channel blockers

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