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Pertti J Neuvonen - One of the best experts on this subject based on the ideXlab platform.
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orange juice substantially reduces the bioavailability of the β adrenergic blocking agent Celiprolol
Clinical Pharmacology & Therapeutics, 2004Co-Authors: Jari J Lilja, Laura Junttipatinen, Pertti J NeuvonenAbstract:Background Grapefruit juice was recently found to decrease plasma concentrations of the β-adrenergic receptor–blocking agent Celiprolol. Our objective was to investigate the effect of orange juice on the pharmacokinetics of Celiprolol in healthy subjects. Methods In a randomized crossover study with 2 phases and a washout of 2 weeks, 10 healthy volunteers ingested either 200 mL normal-strength orange juice or water 3 times a day for 2 days. On the morning of day 3, 1 hour after ingestion of 200 mL orange juice or water, each subject ingested 100 mg Celiprolol with either 200 mL orange juice or water. In addition, 200 mL orange juice or water was ingested at 4, 10, 22, and 27 hours after Celiprolol intake. The concentrations of Celiprolol in plasma and its excretion into urine were measured up to 33 hours after its dosing. Systolic and diastolic blood pressures and heart rate were recorded up to 10 hours. Results Orange juice reduced the mean peak plasma concentration of Celiprolol by 89% (P < .01) and the mean area under the plasma Celiprolol concentration–time curve by 83% (P < .01). The time to peak concentration of Celiprolol increased from 4 to 6 hours (P < .05), and the half-life was prolonged from 4.6 to 10.8 hours (P = .05) after ingestion of orange juice. Orange juice reduced the urinary excretion of Celiprolol by 77% (P < .01). No significant differences were observed in the hemodynamic variables between the phases. Conclusions Orange juice substantially reduces the bioavailability of Celiprolol, but the mechanism of this interaction remains to be resolved. For example, modulation of intestinal pH and of function of transporters implicated in the absorption of Celiprolol may be involved. Because of the great extent of the orange juice–Celiprolol interaction and a wide use of orange juice, this interaction is likely to have clinical importance in some patients, although hemodynamic consequences were not seen in young healthy subjects. Clinical Pharmacology & Therapeutics (2004) 75, 184–190; doi: 10.1016/j.clpt.2003.11.002
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Orange juice substantially reduces the bioavailability of the β‐adrenergic–blocking agent Celiprolol
Clinical pharmacology and therapeutics, 2004Co-Authors: Jari J Lilja, Laura Juntti‐patinen, Pertti J NeuvonenAbstract:Background Grapefruit juice was recently found to decrease plasma concentrations of the β-adrenergic receptor–blocking agent Celiprolol. Our objective was to investigate the effect of orange juice on the pharmacokinetics of Celiprolol in healthy subjects. Methods In a randomized crossover study with 2 phases and a washout of 2 weeks, 10 healthy volunteers ingested either 200 mL normal-strength orange juice or water 3 times a day for 2 days. On the morning of day 3, 1 hour after ingestion of 200 mL orange juice or water, each subject ingested 100 mg Celiprolol with either 200 mL orange juice or water. In addition, 200 mL orange juice or water was ingested at 4, 10, 22, and 27 hours after Celiprolol intake. The concentrations of Celiprolol in plasma and its excretion into urine were measured up to 33 hours after its dosing. Systolic and diastolic blood pressures and heart rate were recorded up to 10 hours. Results Orange juice reduced the mean peak plasma concentration of Celiprolol by 89% (P < .01) and the mean area under the plasma Celiprolol concentration–time curve by 83% (P < .01). The time to peak concentration of Celiprolol increased from 4 to 6 hours (P < .05), and the half-life was prolonged from 4.6 to 10.8 hours (P = .05) after ingestion of orange juice. Orange juice reduced the urinary excretion of Celiprolol by 77% (P < .01). No significant differences were observed in the hemodynamic variables between the phases. Conclusions Orange juice substantially reduces the bioavailability of Celiprolol, but the mechanism of this interaction remains to be resolved. For example, modulation of intestinal pH and of function of transporters implicated in the absorption of Celiprolol may be involved. Because of the great extent of the orange juice–Celiprolol interaction and a wide use of orange juice, this interaction is likely to have clinical importance in some patients, although hemodynamic consequences were not seen in young healthy subjects. Clinical Pharmacology & Therapeutics (2004) 75, 184–190; doi: 10.1016/j.clpt.2003.11.002
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rifampicin reduces plasma concentrations of Celiprolol
European Journal of Clinical Pharmacology, 2004Co-Authors: Jari J Lilja, Mikko Niemi, Pertti J NeuvonenAbstract:Objective The β-adrenoceptor-blocking agent Celiprolol undergoes negligible metabolism, but is a substrate for P-glycoprotein. Our objective was to investigate the effects of rifampicin on the pharmacokinetics of Celiprolol in healthy subjects.
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Rifampicin reduces plasma concentrations of Celiprolol.
European journal of clinical pharmacology, 2003Co-Authors: Jari J Lilja, Mikko Niemi, Pertti J NeuvonenAbstract:The beta-adrenoceptor-blocking agent Celiprolol undergoes negligible metabolism, but is a substrate for P-glycoprotein. Our objective was to investigate the effects of rifampicin on the pharmacokinetics of Celiprolol in healthy subjects. In a randomized cross-over study with two phases and a washout of 4 weeks, ten healthy volunteers received a 5-day pretreatment with rifampicin (600 mg daily) or placebo. On day 6, a single 200-mg dose of Celiprolol was administered orally. The plasma concentrations of Celiprolol and the excretion of Celiprolol into urine were measured up to 33 h after its dosing. Systolic and diastolic blood pressures and heart rate were recorded in a sitting position before the administration of Celiprolol and 2, 4, 6, and 10 h later. MDR1 (P-glycoprotein) genotype was assessed with respect to polymorphisms in exon 21 (G2677T/A) and in exon 26 (C3435T). Rifampicin pretreatment reduced the median area under the plasma Celiprolol concentration-time curve AUC(0-33 h) to 0.44-fold [90% confidence interval (CI), 0.27-0.86], relative to the placebo. The median peak plasma concentration, the time of peak concentration, and the elimination half-life of Celiprolol were not significantly changed by rifampicin. During the rifampicin phase, the median amount of Celiprolol excreted into urine was decreased by 47% ( P<0.05) and Celiprolol renal clearance increased by 19% ( P<0.05) compared with the placebo phase. There were great inter-individual differences in the extent of rifampicin-Celiprolol interaction. However, no association was found between the MDR1 polymorphisms and the degree of interaction between rifampicin and Celiprolol. No significant differences were observed in hemodynamic parameters between the phases. Rifampicin pretreatment reduces plasma Celiprolol concentrations, possibly by induction of the efflux transporter P-glycoprotein, particularly in the intestinal wall, which leads to decreased absorption of Celiprolol.
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itraconazole increases but grapefruit juice greatly decreases plasma concentrations of Celiprolol
Clinical Pharmacology & Therapeutics, 2003Co-Authors: Jari J Lilja, Janne T Backman, Jouko Laitila, Harri Luurila, Pertti J NeuvonenAbstract:Objectives Our objective was to evaluate the effects of itraconazole and grapefruit juice on the pharmacokinetics of the β-adrenergic receptor-blocking agent Celiprolol in healthy volunteers. Methods In a randomized 3-phase crossover study, 12 healthy volunteers took itraconazole 200 mg orally or placebo twice a day or 200 mL grapefruit juice 3 times a day for 2 days. On the morning of day 3, 1 hour after ingestion of itraconazole, placebo, or grapefruit juice, each subject ingested 100 mg Celiprolol with 200 mL of water (placebo and itraconazole phases) or grapefruit juice. In addition, 200 mL of water or grapefruit juice was ingested 4 and 10 hours after Celiprolol intake. The plasma concentrations of Celiprolol, itraconazole, and hydroxyitraconazole and the excretion of Celiprolol into urine were measured up to 33 hours after dosing. Systolic and diastolic blood pressures and heart rate were recorded with subjects in a sitting position before the administration of Celiprolol and 2, 4, 6, and 10 hours later. Results During the itraconazole phase, the mean area under the plasma concentration-time curve from 0 to 33 hours [AUC(0–33)] of Celiprolol was 80% greater (P < .05) than in the placebo phase. During the grapefruit juice phase, the mean AUC(0–33) and peak plasma concentration values of Celiprolol were reduced to about 13% (P < .001) and 5% (P < .001) of the respective placebo phase values. The cumulative excretion into urine of Celiprolol was increased by 59% by itraconazole (P < .05) and decreased by 85% by grapefruit juice (P < .001). Hemodynamic variables did not differ between the phases. Conclusions Itraconazole almost doubles but grapefruit juice greatly reduces plasma concentrations of Celiprolol. The itraconazole-Celiprolol interaction most likely resulted from increased absorption of Celiprolol possibly as a result of P-glycoprotein inhibition in the intestine. The reduced Celiprolol concentrations during the grapefruit juice phase were probably caused by physicochemical factors that interfered with Celiprolol absorption, although other mechanisms cannot be excluded. The grapefruit juice-Celiprolol interaction is probably of clinical relevance. Clinical Pharmacology & Therapeutics (2003) 73, 192–198; doi: 10.1067/mcp.2003.26
Martin J. Kendall - One of the best experts on this subject based on the ideXlab platform.
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Exercise metabolism in healthy volunteers taking Celiprolol, atenolol, and placebo.
British journal of sports medicine, 1997Co-Authors: A Head, S Maxwell, Martin J. KendallAbstract:Previous studies have shown that beta 1 selective agents have fewer adverse effects on exercise metabolism than nonselective beta blockers, and this has been attributed to their reduced blockade of beta 2 receptors. This study aimed at determining whether a beta blocker with partial agonist activity at beta 1 and beta 2 receptors (Celiprolol) was better than a conventional beta 1 receptor-blocker (atenolol) in prolonging exercise capabilities. After four days of treatment with Celiprolol 200 mg, atenolol 50 mg, or placebo, 22 healthy volunteers exercised on a treadmill for two hours at 50% of their maximal oxygen uptake. Resting heart rate and blood pressure were recorded before and after exercise. During exercise, fat oxidation, plasma free fatty acids, glycerol, glucose, and ammonia were measured together with heart rate and perceived exertion. Mean exercising heart rate was significantly lower in those taking either of the beta blockers than in those taking placebo, and significantly lower for those taking atenolol rather than Celiprolol. Fat oxidation was significantly lower for those taking Celiprolol (38.8 (SD 12.2)%, P < 0.01) and atenolol (36.6 (15.9)%, P < 0.01) compared with placebo (45.6 (14.1)%). For the first 15 minutes of exercise, fat oxidation was significantly lower for those taking atenolol (24.6 (12.8)%, P < 0.01) than Celiprolol (29.6 (14.3)%). The rise in plasma free fatty acids and glycerol during exercise was also significantly attenuated by both beta blockers in comparison with the rise in those taking placebo (P < 0.01). Both Celiprolol and atenolol reduced fat oxidation compared with placebo. For the first 15 minutes of exercise fat oxidation was preserved by Celiprolol, but not atenolol. This preservation of fat oxidation during the early part of exercise may confer some small benefit to patients who take beta blockers and intend to exercise regularly. However, we did not detect significant differences between atenolol and Celiprolol in overall mean fat oxidation or perceived exertion in this study.
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exercise metabolism in healthy volunteers taking Celiprolol atenolol and placebo
British Journal of Sports Medicine, 1997Co-Authors: A Head, S Maxwell, Martin J. KendallAbstract:OBJECTIVE: Previous studies have shown that beta 1 selective agents have fewer adverse effects on exercise metabolism than nonselective beta blockers, and this has been attributed to their reduced blockade of beta 2 receptors. This study aimed at determining whether a beta blocker with partial agonist activity at beta 1 and beta 2 receptors (Celiprolol) was better than a conventional beta 1 receptor-blocker (atenolol) in prolonging exercise capabilities. METHODS: After four days of treatment with Celiprolol 200 mg, atenolol 50 mg, or placebo, 22 healthy volunteers exercised on a treadmill for two hours at 50% of their maximal oxygen uptake. Resting heart rate and blood pressure were recorded before and after exercise. During exercise, fat oxidation, plasma free fatty acids, glycerol, glucose, and ammonia were measured together with heart rate and perceived exertion. RESULTS: Mean exercising heart rate was significantly lower in those taking either of the beta blockers than in those taking placebo, and significantly lower for those taking atenolol rather than Celiprolol. Fat oxidation was significantly lower for those taking Celiprolol (38.8 (SD 12.2)%, P < 0.01) and atenolol (36.6 (15.9)%, P < 0.01) compared with placebo (45.6 (14.1)%). For the first 15 minutes of exercise, fat oxidation was significantly lower for those taking atenolol (24.6 (12.8)%, P < 0.01) than Celiprolol (29.6 (14.3)%). The rise in plasma free fatty acids and glycerol during exercise was also significantly attenuated by both beta blockers in comparison with the rise in those taking placebo (P < 0.01). CONCLUSIONS: Both Celiprolol and atenolol reduced fat oxidation compared with placebo. For the first 15 minutes of exercise fat oxidation was preserved by Celiprolol, but not atenolol. This preservation of fat oxidation during the early part of exercise may confer some small benefit to patients who take beta blockers and intend to exercise regularly. However, we did not detect significant differences between atenolol and Celiprolol in overall mean fat oxidation or perceived exertion in this study.
Jari J Lilja - One of the best experts on this subject based on the ideXlab platform.
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orange juice substantially reduces the bioavailability of the β adrenergic blocking agent Celiprolol
Clinical Pharmacology & Therapeutics, 2004Co-Authors: Jari J Lilja, Laura Junttipatinen, Pertti J NeuvonenAbstract:Background Grapefruit juice was recently found to decrease plasma concentrations of the β-adrenergic receptor–blocking agent Celiprolol. Our objective was to investigate the effect of orange juice on the pharmacokinetics of Celiprolol in healthy subjects. Methods In a randomized crossover study with 2 phases and a washout of 2 weeks, 10 healthy volunteers ingested either 200 mL normal-strength orange juice or water 3 times a day for 2 days. On the morning of day 3, 1 hour after ingestion of 200 mL orange juice or water, each subject ingested 100 mg Celiprolol with either 200 mL orange juice or water. In addition, 200 mL orange juice or water was ingested at 4, 10, 22, and 27 hours after Celiprolol intake. The concentrations of Celiprolol in plasma and its excretion into urine were measured up to 33 hours after its dosing. Systolic and diastolic blood pressures and heart rate were recorded up to 10 hours. Results Orange juice reduced the mean peak plasma concentration of Celiprolol by 89% (P < .01) and the mean area under the plasma Celiprolol concentration–time curve by 83% (P < .01). The time to peak concentration of Celiprolol increased from 4 to 6 hours (P < .05), and the half-life was prolonged from 4.6 to 10.8 hours (P = .05) after ingestion of orange juice. Orange juice reduced the urinary excretion of Celiprolol by 77% (P < .01). No significant differences were observed in the hemodynamic variables between the phases. Conclusions Orange juice substantially reduces the bioavailability of Celiprolol, but the mechanism of this interaction remains to be resolved. For example, modulation of intestinal pH and of function of transporters implicated in the absorption of Celiprolol may be involved. Because of the great extent of the orange juice–Celiprolol interaction and a wide use of orange juice, this interaction is likely to have clinical importance in some patients, although hemodynamic consequences were not seen in young healthy subjects. Clinical Pharmacology & Therapeutics (2004) 75, 184–190; doi: 10.1016/j.clpt.2003.11.002
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Orange juice substantially reduces the bioavailability of the β‐adrenergic–blocking agent Celiprolol
Clinical pharmacology and therapeutics, 2004Co-Authors: Jari J Lilja, Laura Juntti‐patinen, Pertti J NeuvonenAbstract:Background Grapefruit juice was recently found to decrease plasma concentrations of the β-adrenergic receptor–blocking agent Celiprolol. Our objective was to investigate the effect of orange juice on the pharmacokinetics of Celiprolol in healthy subjects. Methods In a randomized crossover study with 2 phases and a washout of 2 weeks, 10 healthy volunteers ingested either 200 mL normal-strength orange juice or water 3 times a day for 2 days. On the morning of day 3, 1 hour after ingestion of 200 mL orange juice or water, each subject ingested 100 mg Celiprolol with either 200 mL orange juice or water. In addition, 200 mL orange juice or water was ingested at 4, 10, 22, and 27 hours after Celiprolol intake. The concentrations of Celiprolol in plasma and its excretion into urine were measured up to 33 hours after its dosing. Systolic and diastolic blood pressures and heart rate were recorded up to 10 hours. Results Orange juice reduced the mean peak plasma concentration of Celiprolol by 89% (P < .01) and the mean area under the plasma Celiprolol concentration–time curve by 83% (P < .01). The time to peak concentration of Celiprolol increased from 4 to 6 hours (P < .05), and the half-life was prolonged from 4.6 to 10.8 hours (P = .05) after ingestion of orange juice. Orange juice reduced the urinary excretion of Celiprolol by 77% (P < .01). No significant differences were observed in the hemodynamic variables between the phases. Conclusions Orange juice substantially reduces the bioavailability of Celiprolol, but the mechanism of this interaction remains to be resolved. For example, modulation of intestinal pH and of function of transporters implicated in the absorption of Celiprolol may be involved. Because of the great extent of the orange juice–Celiprolol interaction and a wide use of orange juice, this interaction is likely to have clinical importance in some patients, although hemodynamic consequences were not seen in young healthy subjects. Clinical Pharmacology & Therapeutics (2004) 75, 184–190; doi: 10.1016/j.clpt.2003.11.002
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rifampicin reduces plasma concentrations of Celiprolol
European Journal of Clinical Pharmacology, 2004Co-Authors: Jari J Lilja, Mikko Niemi, Pertti J NeuvonenAbstract:Objective The β-adrenoceptor-blocking agent Celiprolol undergoes negligible metabolism, but is a substrate for P-glycoprotein. Our objective was to investigate the effects of rifampicin on the pharmacokinetics of Celiprolol in healthy subjects.
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Rifampicin reduces plasma concentrations of Celiprolol.
European journal of clinical pharmacology, 2003Co-Authors: Jari J Lilja, Mikko Niemi, Pertti J NeuvonenAbstract:The beta-adrenoceptor-blocking agent Celiprolol undergoes negligible metabolism, but is a substrate for P-glycoprotein. Our objective was to investigate the effects of rifampicin on the pharmacokinetics of Celiprolol in healthy subjects. In a randomized cross-over study with two phases and a washout of 4 weeks, ten healthy volunteers received a 5-day pretreatment with rifampicin (600 mg daily) or placebo. On day 6, a single 200-mg dose of Celiprolol was administered orally. The plasma concentrations of Celiprolol and the excretion of Celiprolol into urine were measured up to 33 h after its dosing. Systolic and diastolic blood pressures and heart rate were recorded in a sitting position before the administration of Celiprolol and 2, 4, 6, and 10 h later. MDR1 (P-glycoprotein) genotype was assessed with respect to polymorphisms in exon 21 (G2677T/A) and in exon 26 (C3435T). Rifampicin pretreatment reduced the median area under the plasma Celiprolol concentration-time curve AUC(0-33 h) to 0.44-fold [90% confidence interval (CI), 0.27-0.86], relative to the placebo. The median peak plasma concentration, the time of peak concentration, and the elimination half-life of Celiprolol were not significantly changed by rifampicin. During the rifampicin phase, the median amount of Celiprolol excreted into urine was decreased by 47% ( P<0.05) and Celiprolol renal clearance increased by 19% ( P<0.05) compared with the placebo phase. There were great inter-individual differences in the extent of rifampicin-Celiprolol interaction. However, no association was found between the MDR1 polymorphisms and the degree of interaction between rifampicin and Celiprolol. No significant differences were observed in hemodynamic parameters between the phases. Rifampicin pretreatment reduces plasma Celiprolol concentrations, possibly by induction of the efflux transporter P-glycoprotein, particularly in the intestinal wall, which leads to decreased absorption of Celiprolol.
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itraconazole increases but grapefruit juice greatly decreases plasma concentrations of Celiprolol
Clinical Pharmacology & Therapeutics, 2003Co-Authors: Jari J Lilja, Janne T Backman, Jouko Laitila, Harri Luurila, Pertti J NeuvonenAbstract:Objectives Our objective was to evaluate the effects of itraconazole and grapefruit juice on the pharmacokinetics of the β-adrenergic receptor-blocking agent Celiprolol in healthy volunteers. Methods In a randomized 3-phase crossover study, 12 healthy volunteers took itraconazole 200 mg orally or placebo twice a day or 200 mL grapefruit juice 3 times a day for 2 days. On the morning of day 3, 1 hour after ingestion of itraconazole, placebo, or grapefruit juice, each subject ingested 100 mg Celiprolol with 200 mL of water (placebo and itraconazole phases) or grapefruit juice. In addition, 200 mL of water or grapefruit juice was ingested 4 and 10 hours after Celiprolol intake. The plasma concentrations of Celiprolol, itraconazole, and hydroxyitraconazole and the excretion of Celiprolol into urine were measured up to 33 hours after dosing. Systolic and diastolic blood pressures and heart rate were recorded with subjects in a sitting position before the administration of Celiprolol and 2, 4, 6, and 10 hours later. Results During the itraconazole phase, the mean area under the plasma concentration-time curve from 0 to 33 hours [AUC(0–33)] of Celiprolol was 80% greater (P < .05) than in the placebo phase. During the grapefruit juice phase, the mean AUC(0–33) and peak plasma concentration values of Celiprolol were reduced to about 13% (P < .001) and 5% (P < .001) of the respective placebo phase values. The cumulative excretion into urine of Celiprolol was increased by 59% by itraconazole (P < .05) and decreased by 85% by grapefruit juice (P < .001). Hemodynamic variables did not differ between the phases. Conclusions Itraconazole almost doubles but grapefruit juice greatly reduces plasma concentrations of Celiprolol. The itraconazole-Celiprolol interaction most likely resulted from increased absorption of Celiprolol possibly as a result of P-glycoprotein inhibition in the intestine. The reduced Celiprolol concentrations during the grapefruit juice phase were probably caused by physicochemical factors that interfered with Celiprolol absorption, although other mechanisms cannot be excluded. The grapefruit juice-Celiprolol interaction is probably of clinical relevance. Clinical Pharmacology & Therapeutics (2003) 73, 192–198; doi: 10.1067/mcp.2003.26
A Head - One of the best experts on this subject based on the ideXlab platform.
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Exercise metabolism in healthy volunteers taking Celiprolol, atenolol, and placebo.
British journal of sports medicine, 1997Co-Authors: A Head, S Maxwell, Martin J. KendallAbstract:Previous studies have shown that beta 1 selective agents have fewer adverse effects on exercise metabolism than nonselective beta blockers, and this has been attributed to their reduced blockade of beta 2 receptors. This study aimed at determining whether a beta blocker with partial agonist activity at beta 1 and beta 2 receptors (Celiprolol) was better than a conventional beta 1 receptor-blocker (atenolol) in prolonging exercise capabilities. After four days of treatment with Celiprolol 200 mg, atenolol 50 mg, or placebo, 22 healthy volunteers exercised on a treadmill for two hours at 50% of their maximal oxygen uptake. Resting heart rate and blood pressure were recorded before and after exercise. During exercise, fat oxidation, plasma free fatty acids, glycerol, glucose, and ammonia were measured together with heart rate and perceived exertion. Mean exercising heart rate was significantly lower in those taking either of the beta blockers than in those taking placebo, and significantly lower for those taking atenolol rather than Celiprolol. Fat oxidation was significantly lower for those taking Celiprolol (38.8 (SD 12.2)%, P < 0.01) and atenolol (36.6 (15.9)%, P < 0.01) compared with placebo (45.6 (14.1)%). For the first 15 minutes of exercise, fat oxidation was significantly lower for those taking atenolol (24.6 (12.8)%, P < 0.01) than Celiprolol (29.6 (14.3)%). The rise in plasma free fatty acids and glycerol during exercise was also significantly attenuated by both beta blockers in comparison with the rise in those taking placebo (P < 0.01). Both Celiprolol and atenolol reduced fat oxidation compared with placebo. For the first 15 minutes of exercise fat oxidation was preserved by Celiprolol, but not atenolol. This preservation of fat oxidation during the early part of exercise may confer some small benefit to patients who take beta blockers and intend to exercise regularly. However, we did not detect significant differences between atenolol and Celiprolol in overall mean fat oxidation or perceived exertion in this study.
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exercise metabolism in healthy volunteers taking Celiprolol atenolol and placebo
British Journal of Sports Medicine, 1997Co-Authors: A Head, S Maxwell, Martin J. KendallAbstract:OBJECTIVE: Previous studies have shown that beta 1 selective agents have fewer adverse effects on exercise metabolism than nonselective beta blockers, and this has been attributed to their reduced blockade of beta 2 receptors. This study aimed at determining whether a beta blocker with partial agonist activity at beta 1 and beta 2 receptors (Celiprolol) was better than a conventional beta 1 receptor-blocker (atenolol) in prolonging exercise capabilities. METHODS: After four days of treatment with Celiprolol 200 mg, atenolol 50 mg, or placebo, 22 healthy volunteers exercised on a treadmill for two hours at 50% of their maximal oxygen uptake. Resting heart rate and blood pressure were recorded before and after exercise. During exercise, fat oxidation, plasma free fatty acids, glycerol, glucose, and ammonia were measured together with heart rate and perceived exertion. RESULTS: Mean exercising heart rate was significantly lower in those taking either of the beta blockers than in those taking placebo, and significantly lower for those taking atenolol rather than Celiprolol. Fat oxidation was significantly lower for those taking Celiprolol (38.8 (SD 12.2)%, P < 0.01) and atenolol (36.6 (15.9)%, P < 0.01) compared with placebo (45.6 (14.1)%). For the first 15 minutes of exercise, fat oxidation was significantly lower for those taking atenolol (24.6 (12.8)%, P < 0.01) than Celiprolol (29.6 (14.3)%). The rise in plasma free fatty acids and glycerol during exercise was also significantly attenuated by both beta blockers in comparison with the rise in those taking placebo (P < 0.01). CONCLUSIONS: Both Celiprolol and atenolol reduced fat oxidation compared with placebo. For the first 15 minutes of exercise fat oxidation was preserved by Celiprolol, but not atenolol. This preservation of fat oxidation during the early part of exercise may confer some small benefit to patients who take beta blockers and intend to exercise regularly. However, we did not detect significant differences between atenolol and Celiprolol in overall mean fat oxidation or perceived exertion in this study.
Kimihiro Komori - One of the best experts on this subject based on the ideXlab platform.
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Celiprolol reduces the intimal thickening of autogenous vein grafts via an enhancement of nitric oxide function through an inhibition of superoxide production
Journal of Vascular Surgery, 2007Co-Authors: Keisuke Hattori, Dai Yamanouchi, Hiroshi Banno, Masayoshi Kobayashi, Kiyoto Yamamoto, Junko Kajikuri, Takeo Itoh, Kimihiro KomoriAbstract:Background β-adrenoceptor antagonist Celiprolol has been widely used as an effective antihypertensive agent. Some studies reported that Celiprolol enhances nitric oxide production. The purpose of the present study is to examine the effects of Celiprolol on vein graft intimal hyperplasia and endothelium-dependent nitric oxide (NO)-mediated relaxation. Methods Japanese white rabbits were randomized to a control group that was fed regular rabbit chow or to a Celiprolol group that was fed regular rabbit chow supplemented with 100 mg/body Celiprolol sodium. The reversed jugular vein was implanted into the carotid artery. At 2 and 4 weeks after the operation, vein grafts in both groups were harvested, and intimal hyperplasia of the vein grafts was assessed. At 4 weeks after the operation, harvested vein grafts from both the groups were examined on the endothelium-dependent relaxation by application of Ach and were examined to detect for endothelial NO synthase (eNOS) expression and superoxide anion production. Results Celiprolol inhibited intimal hyperplasia of carotid interposition-reversed jugular vein grafts 4 weeks after implantation (Intima/media index of Celiprolol group, 0.48 ± 0.01 vs control group, 1.07 ± 0.08, P Conclusions These novel findings clearly demonstrate that β-adrenoceptor antagonist Celiprolol can suppress intimal hyperplasia of the vein graft, which may be due to the enhancement of nitric oxide function through an inhibition of superoxide production. These results strongly support the clinical usefulness of Celiprolol administration for preventing intimal hyperplasia of the vein graft after bypass grafting.