The inhibitory effect of pluronic on P-glycoprotein drug pump / 药学学报

To investigate the inhibitory effect of Pluronic on P-glycoprotein (P-gp) drug efflux pump, Caco-2 cells and animal models were established to study the influence of Pluronic on celiprolol transport across Caco-2 cell monolayer and intestinal mucous membrane with verapamil set as a positive control. Drug concentration was measured by HPLC and the apparent permeability coefficient (P(app)), absorption rate constant (k(a)) and the effective permeability coefficient (P(eff)) were calculated. P(app) of basolateral to apical side and apical to basolateral side was (2.10 +/- 0.13) x 10(-6) and (0.333 +/- 0.018) x 10(-6) cm x s(-1), respectively. Transports of celiprolol across Caco-2 cell monolayer were influenced by both verapamil and Pluronic. The absorption constants (k(a)) of celiprolol at duodenum, jejunum, ileum, and colon were (0.09 +/- 0.03), (0.14 +/- 0.04), (0.11 +/- 0.03) and (0.05 +/- 0.02) h(-1), k(a) of celiprolol in verapamil group were (0.14 +/- 0.03), (0.24 +/- 0.02), (0.25 +/- 0.03) and (0.23 +/- 0.02) h(-1), and k(a) of celiprolol in Pluronic group were (0.13 +/- 0.02), (0.22 +/- 0.02), (0.22 +/- 0.03) and (0.20 +/- 0.03) h(-1), respectively. Pluronic showed significant effect on inhibiting P-gp of Caco-2 cell and intestinal mucosa in rats.

Seguridad y eficacia de celiprolol en hipertensos con enfermedad pulmonar obstructiva crónica / Safety and efficacy of celiprolol in patients with chronic obstructive lung disease

Background: Third generation beta blockers have an intrinsic simpatico-mimetic activity and are cardioselective. Therefore, they should not have adverse bronchial effects and could even have a slight bronchodilator activity. Aim: To test the efficacy and safety of celiprolol in hypertensive patients with chronic obstructive lung disease. Patients and methods: Uncomplicated hypertensive patients with chronic obstructive lung disease received celiprolol during 12 weeks. They were subjected to monthly clinical assessment and ventilatory function was measured on the basal period and at the end of the trial. Results: During the study period, blood pressure fell significantly from 179ñ6/112ñ8 to 161ñ4,7/98ñ1.6 mmHg. No changes were observed in forced expiratory volume in 1 s or in forced expiratory flow between 25 and 75 percent of the vital capacity. No subjective changes in respiratory function were reported during the trial. Conclusions: No changes in ventilatory function were observed in these patients with chronic obstructive lung disease, treated with celiprolol during 12 weeks

Beta-blockers and renal ablated rats

This study was conducted to compare the effects of carvedilol, celiprolol and propranolol on some renal function parameters, oxidative stress profile and histopathological features in renal ablated rats and to evaluate the effects of supplementation of celiprolol or propranolol treatment with vitamin E on the previously mentioned parameters. It was concluded that vasodilator beta-blockers with antioxidant activity as carvedilol offered renoprotective effects more than propranolol. Carvedilol exhibited an increasing histopathological and functional end-organ protection in renal ablated rats. The reduction of plasma renin activity and lipid peroxidation may contribute to its renoprotective effects. The addition of vitamin E to celiprolol or propranolol treatment was mandatory to improve renal function and lipid peroxidation in partially ablated rats

Celiprolol versus metoprolol and propranolol on vascular reactivity and serum lipid profile in experimental animals

In the present study, the effects of the 2 cardioselective beta-adrenoceptive blockers; celiprolol and metoprolol on serum lipid profile and on the isolated aortic strip were investigated in comparison with the standard non-selective beta-blocker propranolol. The influence of the 3 beta-blockers on serum lipid profile was determined by measuring the total triglycerides [TG], total cholesterol [TG,], high density lipoprotein cholesterol [HDL-C], and low density lipoprotein cholesterol [LDL-C] in serum of adult male albino rats. Celiprolol [40 mg/kg] metoprolol [l0 mg/kg,]; and propranolol [10mg/kg]; were given orally once daily to adult rats for 2 months. Statistical analysis of the results revealed that celiprolol significantly decreased the serum levels of TG; TC; LDL-C; and significantly increased HDL-C serum levels. While, metoprolol induced insignificant changes in serum lipid profile. On the other hand, propranolol was found to significantly increase LDL-G; TG; and TC levels, while it significantly decreased HDL-C level. On the isolated rabbit aortic strip, the addition of celiprolol [l6ug/ml bath] was found to significantly decrease the contractile response of the aortic strip to different concentrations of phenylephrine. Metoprolol and propranolol, on the other hand, were found to induce insignificant changes on the contractile responses of the isolated rabbit aortic strip to phenylephrine. So, celiprolol might be a suitable alternative to the currently used cadioselective BB; when the issues of hyperlipidemia and quality of life are to be dealt with in a hypertensive cardiac patient

Bioequivalence studies of celiprolol in healthy human volunteers.

Thus bioequivalence between the two products was established by undertaking this study. From table 1 it can be seen that the standard deviation at the various sampling points is high indicating varying absorption rates in individual volunteers, but this was observed in case of both the products. Also, since the study design was complete crossover, this high standard deviation was not due to any study design variable. As celiprolol shows non-linear1 dose related absorption kinetics this high value of standard deviation may be due to the intersubject variation during the absorption process. However all the pharmacokinetic parameters showed a comparable profile when statistically evaluated for any significant difference between the two products.

Clinical Effect and Safety of Celiprolol in Patients with Essential Hypertension

BACKGROUND: Celiprolol is a new generation beta-adrenoreceptor blocking agent with intrinsic sympathomimetic activity characterized by selective blockade of beta1 receptors and partial agonist activity at beta2 receptors. This study was designed to investigate the antihypertensive efficacy and safety of celiprolol in patients with essential hypertension. METHODS: The study subjects consisted of 36 patients(mean age : 55 years, 11 males, 25 females). Celiprolol was administered orally in a aily dose of 200-800mg once or two divided dose for 10 weeks after the admimstration of placebo for 2 weeks. RESULTS: Blood pressure was significantly reduced from 171+/-19/106.8mmHg to 153+/-20/92+/-12mmHg(p<0.01) after 2 week of therapy and this effect was maintained throughout the study periods. The efficacy rates were total 94%(marked improve : 53%, moderate improve : 22%, mild improve : 19%). The cumulative efficacy rate was 72% at 200mg/day, 91% at 400mg/day, and 94% at 800mg/day. Heart rate did not change throughout 10 weeks. There were no significant change in hematologic and blood chemistry variables. During the period of medication, headache developed in 3 cases(8%) and each of dry cough, dyspnea, epigastric pain and diarrhea and facial flushing developed in 1 case(2.8%) but they were tolerable. CONCLUSIONS: This results suggest that celiprolol is effective and safe drug in the treament of patients with essential hypertension.

A Clinical Study on the Antihypertensive Effect of Celiprolol

BACKGROUND: Celiprolol is a beta-adrenergic blocker characterized by selective blokade of beta1 receptors and partial agonist activity at beta2 receptors. This study was designed to evaluate the antihypertensive efficacy, metabolic effects and safety of celiprolol in patients with essential hypertension. METHODS: Celiprolol 200mg was administered once daily in 20 hypertensive Korean adults(9 males and 11 females) for ten weeks with dose titration every 2 weeks. RESULTS: The supine blood pressure was decreased from 168.8+/-20.6/106.5/12.0mmHg(mean/S.D) to 131.2+/-12.8/88.2+/-7.9mmHg at the end treatment(P<0.05). Heart rate was not changed significantly throughout the period. Total cholesterol(TC) was decreased from 211.3+/-12.6mg/dl to 186.7+/-10.4mg/dl(P<0.05) and triglyceride(TG) from 223.7+/-24.5mg/dl to 198.4+/-12.9mg/dl after 10 weeks treatment(P<0.05). LDL(low-density lipoprotein)-cholesterol was decreased from 126.4+/-13.4mg/dl to 118.5+/-12.3mg/dl after 10 weeks treatment(P<0.05). During the period of the study, headache and fatigue developed in a few patient but were not troublesome enough to stop medication. CONCLUSIONS: Celiprolol 200mg once daily regimen was well tolerated and effective in the treatment of essential hypertensiove patients with favorable effects on blood lipids.