The Experts below are selected from a list of 162 Experts worldwide ranked by ideXlab platform
Martina Felder - One of the best experts on this subject based on the ideXlab platform.
-
long term results of a clinical trial of Nadolol with or without isosorbide mononitrate for primary prophylaxis of variceal bleeding in cirrhosis
Hepatology, 2000Co-Authors: Carlo Merkel, Carole Donada, Giorgio Cavallarin, Pierluigi Torboli, Giuliana Sebastianelli, Massimo Bolognesi, R. Marin, Piero Amodio, David Sacerdoti, Martina FelderAbstract:It is clearly established that beta-blockers decrease the risk of a first variceal bleeding in cirrhosis. We have recently shown that the addition of isosorbide mononitrate to Nadolol decreases the rate of variceal bleeding in patients with cirrhosis and varices, compared with Nadolol alone, after a median follow-up of 30 months. It is not established if the long-term treatment with the combination continues to be beneficial. Therefore, we assessed the long-term effect of this combination on first variceal bleeding, complications, and death. One hundred forty-six cirrhotic patients with esophageal varices included in a previously published multicenter, randomized study comparing Nadolol (40-160 mg/d) with the combination Nadolol plus isosorbide mononitrate (10-20 mg 3 times per day) were followed up for up to 7 years (median follow-up, 55 months). The primary end-point was variceal bleeding of any severity. Twenty-four patients (16 in the Nadolol group, and 8 in the combination group) experienced variceal bleeding (log rank test, P =.02). Cumulative risk of bleeding was 29% and 12%, respectively (95% CI for the difference, 1%-23%). Two and 4 patients, respectively, had bleeding from portal hypertensive gastropathy (log rank test, P =.20). Thirty and 25 patients, respectively, died during follow-up (log rank test, P =.13). Twelve and 10 patients, respectively, had de novo occurrence of ascites during follow-up (log rank test, P =.29). In conclusion, Nadolol plus isosorbide mononitrate is significantly more effective than Nadolol alone in the long-term use. Side effects are few, and no deleterious effects on ascites occurrence or on survival occur after long-term use of this combination.
-
long term results of a clinical trial of Nadolol with or without isosorbide mononitrate for primary prophylaxis of variceal bleeding in cirrhosis
Hepatology, 2000Co-Authors: Carlo Merkel, Carole Donada, Giorgio Cavallarin, Pierluigi Torboli, Giuliana Sebastianelli, Massimo Bolognesi, R. Marin, Piero Amodio, David Sacerdoti, Martina FelderAbstract:It is clearly established that β-blockers decrease the risk of a first variceal bleeding in cirrhosis. We have recently shown that the addition of isosorbide mononitrate to Nadolol decreases the rate of variceal bleeding in patients with cirrhosis and varices, compared with Nadolol alone, after a median follow-up of 30 months. It is not established if the long-term treatment with the combination continues to be beneficial. Therefore, we assessed the long-term effect of this combination on first variceal bleeding, complications, and death. One hundred forty-six cirrhotic patients with esophageal varices included in a previously published multicenter, randomized study comparing Nadolol (40-160 mg/d) with the combination Nadolol plus isosorbide mononitrate (10-20 mg 3 times per day) were followed up for up to 7 years (median follow-up, 55 months). The primary end-point was variceal bleeding of any severity. Twenty-four patients (16 in the Nadolol group, and 8 in the combination group) experienced variceal bleeding (log rank test, P = .02). Cumulative risk of bleeding was 29% and 12%, respectively (95% CI for the difference, 1%-23%). Two and 4 patients, respectively, had bleeding from portal hypertensive gastropathy (log rank test, P = .20). Thirty and 25 patients, respectively, died during follow-up (log rank test, P = .13). Twelve and 10 patients, respectively, had de novo occurrence of ascites during follow-up (log rank test, P = .29). In conclusion, Nadolol plus isosorbide mononitrate is significantly more effective than Nadolol alone in the long-term use. Side effects are few, and no deleterious effects on ascites occurrence or on survival occur after long-term use of this combination.
-
randomised trial of Nadolol alone or with isosorbide mononitrate for primary prophylaxis of variceal bleeding in cirrhosis
The Lancet, 1996Co-Authors: Carlo Merkel, E Enzo, Carole Donada, Giorgio Cavallarin, Pierluigi Torboli, Giuliana Sebastianelli, R. Marin, Piero Amodio, David Sacerdoti, Martina FelderAbstract:Summary Background The risk of having a first cirrhosis-associated variceal bleed is lowered by about 50% by β-blockers. Use of β-blockers is currently recommended for patients with cirrhosis and oesophageal varices that are at risk of bleeding. We aimed to test the effectiveness of isosorbide mononitrate as an adjunct to the β-blocker Nadolol in the prophylaxis of first variceal bleeding in these patients. Methods We did a randomised multicentre study to compare the non-selective β -blocker, Nadolol, with Nadolol plus isosorbide mononitrate in 146 relatively well (Child-Pugh score ≤11) patients who had oesophageal varices at risk of bleeding. Patients on Nadolol alone received a single oral 40 mg daily dose. Every second day the dose was titrated to achieve 20–25% decrease in resting heart rate (maximum dose 160 mg daily). Patients receiving both drugs received Nadolol as above then isosorbide mononitrate was added starting with 10 mg orally twice daily, which was increased to 20 mg unless hypotension or severe headache occurred. The main endpoint was the occurrence of variceal bleeding of any severity. Patients were followed up for up to 40 months. Findings During the study period 11 of 74 patients from the Nadolol alone group and four of 72 from the nadalol plus isosorbide mononitrate group had variceal bleeding (logrank test p=0·03). Cumulative risk of variceal bleeding was 18% in the Nadolol group and 7·5% in the combined treatment group (95% CI for difference 1–25%). Two patients in each group had a non-variceal bleed related to portal hypertension. 14 patients from the Nadolol only group and eight from the combined treatment group died during the study period (log-rank test p=0·09). Four and eight patients, respectively, had to discontinue one of the drugs because of side-effects. Interpretation Nadolol plus isosorbide mononitrate is signifcantly more effective than Nadolol alone in the primary prophylaxis of variceal bleeding in relatively well patients with cirrhosis, and has few side-effects.
Shingen Misaka - One of the best experts on this subject based on the ideXlab platform.
-
Urinary Excretion of Nadolol as a Possible In Vivo Probe for Drug Interactions Involving P-Glycoprotein.
Journal of clinical pharmacology, 2021Co-Authors: Sho Shimazaki, Kenju Shimomura, Junko Kuroda, Shingen MisakaAbstract:Nadolol is a hydrophilic and non-selective β-adrenoceptor blocker with a bioavailability of 30%, relatively longer half-life, negligible metabolism, and predominant renal excretion. Previous studies have reported that Nadolol is a substrate of P-glycoprotein, and the coadministration with itraconazole, a typical P-glycoprotein inhibitor, results in elevated plasma concentrations and cumulative urinary excretion of Nadolol. In this study, we assessed whether measurements of urinary-excreted Nadolol can be an alternative method of plasma pharmacokinetics for P-glycoprotein-mediated drug interactions in humans. We re-analyzed the pooled data set of plasma concentration and urinary excretion of Nadolol from our previous clinical studies in a total of 32 healthy Japanese adults. The area under the plasma concentration-time curve from 0 to infinity (AUC0-∞ ) of Nadolol in individual subjects was significantly correlated with the maximum plasma concentration (P < 0.01, r = 0.80), and the cumulative amount excreted into urine (Ae ) at 4 (P = 0.01, r = 0.51), 8 (P < 0.01, r = 0.63), 24 (P < 0.01, r = 0.75), and 48 hours (P < 0.01, r = 0.77). Significant correlations were also observed between the AUC and Ae during the same respective time periods. In the drug interactions of Nadolol with itraconazole, rifampicin, a well-known P-glycoprotein inducer, or grapefruit juice, there were significant correlations between the differences in AUC0-48 and those in Ae, 0-48 from the controls in individual subjects. These results suggest that the measurements of urinary excretion of Nadolol can be employed as a sensitive and reliable alternative to plasma pharmacokinetics for the evaluation of P-glycoprotein-mediated drug interactions. This article is protected by copyright. All rights reserved.
-
Effects of single green tea ingestion on pharmacokinetics of Nadolol in healthy volunteers
British journal of clinical pharmacology, 2020Co-Authors: Shingen Misaka, Osamu Abe, Tomoyuki Ono, Yuko Ono, Hiroshi Ogata, Itaru Miura, Yayoi Shikama, Martin F. Fromm, Hirooki Yabe, Kenju ShimomuraAbstract:Aims The aim of this study was to investigate the effects of a single green tea (GT), administered concomitantly or 1 hour before Nadolol intake on Nadolol pharmacokinetics. Methods In a randomized 3-phase crossover study, 11 healthy volunteers received an oral administration of Nadolol with, or 1 hour after preingestion of brewed GT, or with water in a volume of 150 mL. Results Geometric mean ratio with 90% confidence interval for Nadolol AUC0-48 was 0.371 (0.303-0.439) with concomitant GT. In addition, ingestion of GT 1 hour before Nadolol administration resulted in a significant reduction of Nadolol AUC0-48 with geometric mean ratio of 0.536 (0.406-0.665). There were no differences in time to maximal plasma concentration and renal clearance of Nadolol among groups. Conclusion These results suggest that single concomitant ingestion of GT substantially decreases plasma concentrations of Nadolol. Moreover, the reduction in Nadolol bioavailability could persist for at least 1 hour after drinking a cup of GT.
-
the nonmetabolized β blocker Nadolol is a substrate of oct1 oct2 mate1 mate2 k and p glycoprotein but not of oatp1b1 and oatp1b3
Molecular Pharmaceutics, 2016Co-Authors: Shingen Misaka, Fabian Müller, Hartmut Glaeser, Jana Knop, Katrin Singer, Eva Hoier, Markus Keiser, Jorg Konig, Martin F. FrommAbstract:Nadolol is a nonmetabolized β-adrenoceptor antagonist and is a substrate of OATP1A2, but not of OATP2B1. However, other drug transporters involved in translocation of Nadolol have not been characterized in detail. We therefore investigated Nadolol as a potential substrate of the hepatic uptake transporters OATP1B1, OATP1B3, and OCT1 and of the renal transporters OCT2, MATE1, and MATE2-K expressed in HEK cells. Moreover, the importance of P-glycoprotein (P-gp) for Nadolol transport was studied using double transfected MDCK-OCT1-P-gp cells. Nadolol was not transported by OATP1B1 and OATP1B3. In contrast, a significantly higher Nadolol accumulation (at 1 and 10 μM) was found in OCT1, OCT2, MATE1, and MATE2-K cells compared to control cells (P < 0.01). Km values for OCT2-, MATE1-, and MATE2-K-mediated Nadolol uptake were 122, 531, and 372 μM, respectively. Cimetidine (100 μM, P < 0.01) and trimethoprim (100 μM, P < 0.001) significantly inhibited OCT1-, OCT2-, MATE1-, and MATE2-K-mediated Nadolol transport. The P-gp inhibitor zosuquidar significantly reduced basal to apical Nadolol transport in monolayers of MDCK-OCT1-P-gp cells. In summary, Nadolol is a substrate of the cation transporters OCT1, OCT2, MATE1, MATE2-K, and of P-gp. These data will aid future in vivo studies on potential transporter-mediated drug-drug or drug-food interactions with involvement of Nadolol.
-
Green tea ingestion greatly reduces plasma concentrations of Nadolol in healthy subjects.
Clinical pharmacology and therapeutics, 2014Co-Authors: Shingen Misaka, Junichi Yatabe, Fabian Müller, Kozue Takano, Keisuke Kawabe, Hartmut Glaeser, Midori Yatabe, Satomi Onoue, José Pablo Werba, Hiroshi WatanabeAbstract:This study aimed to evaluate the effects of green tea on the pharmacokinetics and pharmacodynamics of the β-blocker Nadolol. Ten healthy volunteers received a single oral dose of 30 mg Nadolol with green tea or water after repeated consumption of green tea (700 ml/day) or water for 14 days. Catechin concentrations in green tea and plasma were determined. Green tea markedly decreased the maximum plasma concentration (Cmax) and area under the plasma concentration–time curve (AUC0–48) of Nadolol by 85.3% and 85.0%, respectively (P < 0.01), without altering renal clearance of Nadolol. The effects of Nadolol on systolic blood pressure were significantly reduced by green tea. [3H]-Nadolol uptake assays in human embryonic kidney 293 cells stably expressing the organic anion–transporting polypeptides OATP1A2 and OATP2B1 revealed that Nadolol is a substrate of OATP1A2 (Michaelis constant (Km) = 84.3 μmol/l) but not of OATP2B1. Moreover, green tea significantly inhibited OATP1A2-mediated Nadolol uptake (half-maximal inhibitory concentration, IC50 = 1.36%). These results suggest that green tea reduces plasma concentrations of Nadolol possibly in part by inhibition of OATP1A2-mediated uptake of Nadolol in the intestine. Clinical Pharmacology & Therapeutics (2014); 95 4, 432–438. doi:10.1038/clpt.2013.241
-
Effects of green tea extract and (-)-epigallocatechin-3-gallate on pharmacokinetics of Nadolol in rats.
Phytomedicine : international journal of phytotherapy and phytopharmacology, 2013Co-Authors: Shingen Misaka, Nozomu Miyazaki, Tetsuhito Fukushima, Shizuo Yamada, Junko KimuraAbstract:Green tea catechins have been shown to affect the activities of drug transporters in vitro, including P-glycoprotein and organic anion transporting polypeptides. However, it remains unclear whether catechins influence the in vivo disposition of substrate drugs for these transporters. In the present study, we investigated effects of green tea extract (GTE) and (-)-epigallocatechin-3-gallate (EGCG) on pharmacokinetics of a non-selective hydrophilic β-blocker Nadolol, which is reported to be a substrate for several drug transporters and is not metabolized by cytochrome P450 enzymes. Male Sprague-Dawley rats received GTE (400 mg/kg), EGCG (150 mg/kg) or saline (control) by oral gavage, 30 min before a single intragastric administration of 10 mg/kg Nadolol. Plasma and urinary concentrations of Nadolol were determined using high performance liquid chromatography. Pharmacokinetic parameters were estimated by a noncompartmental analysis. Pretreatment with GTE resulted in marked reductions in the maximum concentration (Cmax) and area under the time-plasma concentration curve (AUC) of Nadolol by 85% and 74%, respectively, as compared with control. In addition, EGCG alone significantly reduced Cmax and AUC of Nadolol. Amounts of Nadolol excreted into the urine were decreased by pretreatments with GTE and EGCG, while the terminal half-life of Nadolol was not different among groups. These results suggest that the coadministration with green tea catechins, particularly EGCG, causes a significant alteration in the pharmacokinetics of Nadolol, possibly through the inhibition of its intestinal absorption mediated by uptake transporters.
Carlo Merkel - One of the best experts on this subject based on the ideXlab platform.
-
long term results of a clinical trial of Nadolol with or without isosorbide mononitrate for primary prophylaxis of variceal bleeding in cirrhosis
Hepatology, 2000Co-Authors: Carlo Merkel, Carole Donada, Giorgio Cavallarin, Pierluigi Torboli, Giuliana Sebastianelli, Massimo Bolognesi, R. Marin, Piero Amodio, David Sacerdoti, Martina FelderAbstract:It is clearly established that β-blockers decrease the risk of a first variceal bleeding in cirrhosis. We have recently shown that the addition of isosorbide mononitrate to Nadolol decreases the rate of variceal bleeding in patients with cirrhosis and varices, compared with Nadolol alone, after a median follow-up of 30 months. It is not established if the long-term treatment with the combination continues to be beneficial. Therefore, we assessed the long-term effect of this combination on first variceal bleeding, complications, and death. One hundred forty-six cirrhotic patients with esophageal varices included in a previously published multicenter, randomized study comparing Nadolol (40-160 mg/d) with the combination Nadolol plus isosorbide mononitrate (10-20 mg 3 times per day) were followed up for up to 7 years (median follow-up, 55 months). The primary end-point was variceal bleeding of any severity. Twenty-four patients (16 in the Nadolol group, and 8 in the combination group) experienced variceal bleeding (log rank test, P = .02). Cumulative risk of bleeding was 29% and 12%, respectively (95% CI for the difference, 1%-23%). Two and 4 patients, respectively, had bleeding from portal hypertensive gastropathy (log rank test, P = .20). Thirty and 25 patients, respectively, died during follow-up (log rank test, P = .13). Twelve and 10 patients, respectively, had de novo occurrence of ascites during follow-up (log rank test, P = .29). In conclusion, Nadolol plus isosorbide mononitrate is significantly more effective than Nadolol alone in the long-term use. Side effects are few, and no deleterious effects on ascites occurrence or on survival occur after long-term use of this combination.
-
long term results of a clinical trial of Nadolol with or without isosorbide mononitrate for primary prophylaxis of variceal bleeding in cirrhosis
Hepatology, 2000Co-Authors: Carlo Merkel, Carole Donada, Giorgio Cavallarin, Pierluigi Torboli, Giuliana Sebastianelli, Massimo Bolognesi, R. Marin, Piero Amodio, David Sacerdoti, Martina FelderAbstract:It is clearly established that beta-blockers decrease the risk of a first variceal bleeding in cirrhosis. We have recently shown that the addition of isosorbide mononitrate to Nadolol decreases the rate of variceal bleeding in patients with cirrhosis and varices, compared with Nadolol alone, after a median follow-up of 30 months. It is not established if the long-term treatment with the combination continues to be beneficial. Therefore, we assessed the long-term effect of this combination on first variceal bleeding, complications, and death. One hundred forty-six cirrhotic patients with esophageal varices included in a previously published multicenter, randomized study comparing Nadolol (40-160 mg/d) with the combination Nadolol plus isosorbide mononitrate (10-20 mg 3 times per day) were followed up for up to 7 years (median follow-up, 55 months). The primary end-point was variceal bleeding of any severity. Twenty-four patients (16 in the Nadolol group, and 8 in the combination group) experienced variceal bleeding (log rank test, P =.02). Cumulative risk of bleeding was 29% and 12%, respectively (95% CI for the difference, 1%-23%). Two and 4 patients, respectively, had bleeding from portal hypertensive gastropathy (log rank test, P =.20). Thirty and 25 patients, respectively, died during follow-up (log rank test, P =.13). Twelve and 10 patients, respectively, had de novo occurrence of ascites during follow-up (log rank test, P =.29). In conclusion, Nadolol plus isosorbide mononitrate is significantly more effective than Nadolol alone in the long-term use. Side effects are few, and no deleterious effects on ascites occurrence or on survival occur after long-term use of this combination.
-
hemodynamic evaluation of the addition of isosorbide 5 mononitrate to Nadolol in cirrhotic patients with insufficient response to the beta blocker alone
Hepatology, 1997Co-Authors: Carlo Merkel, E Enzo, Massimo Bolognesi, R. Marin, David Sacerdoti, Giancarlo Bombonato, Paolo Angeli, Angelo GattaAbstract:The association beta-blockers plus isosorbide-5-mononitrate (I5M) has been proposed for the treatment of portal hypertension in patients with insufficient response to beta-blockers alone, according to hemodynamic criteria. The mechanism of action in these patients is not clearly defined. Fifteen patients with cirrhosis and esophageal varices were evaluated by hepatic venous pressure gradient (HVPG) measurement and duplex-Doppler ultrasonography before and after 1 month of treatment with Nadolol. Nine patients who did not exhibit a decrease in HVPG to 12 mm Hg or a percent decrease greater than 20% were classified as poor responders, and were studied again with the same methodology after 3 months of chronic administration of Nadolol + I5M 20 mg twice per day. In poor responders, mean HVPG decrease after Nadolol was 8.9% +/- 2.8%, and after the combination, it was 25.7% +/- 1.7% (P = .004). All patients except one became good responders to the association. Portal blood flow (PBF) decreased significantly after Nadolol (P = .004), and remained unchanged after the addition of nitrates. Resistance to portal blood flow (RPBF) increased after Nadolol (P = .02) and returned to baseline values during combined treatment (P = .03). In good responders, an adequate decrease in HVPG was associated with a decrease in PBF (P = .06) but no change in RPBF. A wide spectrum of combined changes in PBF and in RPBF after Nadolol was observed in poor responders, ranging from no change in either parameter to a marked decrease in PBF counterbalanced by a marked increase in RPBF. The addition of I5M was followed in most cases by larger effects on resistance than on flow. Doppler parameters were not significantly correlated with the HVPG response to Nadolol alone or associated with I5M. It is concluded that good hemodynamic responders to Nadolol differ from poor responders in the lack of increase in RPBF after the drug. The addition of nitrates to Nadolol is effective in decreasing portal pressure in most poor responders to Nadolol alone. A decrease in outflow resistance is the main mechanism involved.
-
randomised trial of Nadolol alone or with isosorbide mononitrate for primary prophylaxis of variceal bleeding in cirrhosis
The Lancet, 1996Co-Authors: Carlo Merkel, E Enzo, Carole Donada, Giorgio Cavallarin, Pierluigi Torboli, Giuliana Sebastianelli, R. Marin, Piero Amodio, David Sacerdoti, Martina FelderAbstract:Summary Background The risk of having a first cirrhosis-associated variceal bleed is lowered by about 50% by β-blockers. Use of β-blockers is currently recommended for patients with cirrhosis and oesophageal varices that are at risk of bleeding. We aimed to test the effectiveness of isosorbide mononitrate as an adjunct to the β-blocker Nadolol in the prophylaxis of first variceal bleeding in these patients. Methods We did a randomised multicentre study to compare the non-selective β -blocker, Nadolol, with Nadolol plus isosorbide mononitrate in 146 relatively well (Child-Pugh score ≤11) patients who had oesophageal varices at risk of bleeding. Patients on Nadolol alone received a single oral 40 mg daily dose. Every second day the dose was titrated to achieve 20–25% decrease in resting heart rate (maximum dose 160 mg daily). Patients receiving both drugs received Nadolol as above then isosorbide mononitrate was added starting with 10 mg orally twice daily, which was increased to 20 mg unless hypotension or severe headache occurred. The main endpoint was the occurrence of variceal bleeding of any severity. Patients were followed up for up to 40 months. Findings During the study period 11 of 74 patients from the Nadolol alone group and four of 72 from the nadalol plus isosorbide mononitrate group had variceal bleeding (logrank test p=0·03). Cumulative risk of variceal bleeding was 18% in the Nadolol group and 7·5% in the combined treatment group (95% CI for difference 1–25%). Two patients in each group had a non-variceal bleed related to portal hypertension. 14 patients from the Nadolol only group and eight from the combined treatment group died during the study period (log-rank test p=0·09). Four and eight patients, respectively, had to discontinue one of the drugs because of side-effects. Interpretation Nadolol plus isosorbide mononitrate is signifcantly more effective than Nadolol alone in the primary prophylaxis of variceal bleeding in relatively well patients with cirrhosis, and has few side-effects.
-
duplex doppler sonographic evaluation of splanchnic and renal effects of single agent and combined therapy with Nadolol and isosorbide 5 mononitrate in cirrhotic patients
Journal of Ultrasound in Medicine, 1994Co-Authors: Massimo Bolognesi, Carlo Merkel, David Sacerdoti, Angelo GattaAbstract:Thirty-eight cirrhotic patients with esophageal varices were investigated by duplex Doppler sonography. In every patient, the portal blood flow mean velocity (cm/sec) and portal blood flow volume (ml/min) were measured. In addition, the pulsatility index [(maximum-minimum)/mean velocity] was measured in the superior mesenteric artery, in the hepatic arteries, in an intrasplenic artery, and in intrarenal arteries. These parameters were measured again 120 to 180 minutes after administration of Nadolol (80 mg orally) in 22 patients, 90 minutes after administration of isosorbide-5-mononitrate (20 mg orally) in nine patients, and subsequently after administration of isosorbide 5-mononitrate to 10 of the 22 patients treated earlier with Nadolol. Duplex Doppler sonographic parameters also were evaluated in seven patients 120 minutes after administration of a placebo. In five of the 22 patients treated acutely with Nadolol, the same parameters were measured again after 60 minutes without any additional drug administration. No hemodynamic changes occurred in response to the placebo. Portal blood flow mean velocity and portal blood flow volume decreased after Nadolol and isosorbide-5-mononitrate; mesenteric pulsatility index increased after both Nadolol and isosorbide-5-mononitrate. After combined therapy, we observed a further reduction in portal blood flow mean velocity and portal blood flow volume and a significant increase in hepatic, splenic, and mesenteric pulsatility indices. The addition of isosorbide-5-mononitrate to Nadolol caused a decrease in portal blood flow mean velocity of more than 17% in all patients. Nadolol caused a slight increase in renal pulsatility index, which was amplified by the addition of isosorbide-5-mononitrate, suggesting a decrease in renal blood flow.
Balasubrahmanyam Chidambaram - One of the best experts on this subject based on the ideXlab platform.
-
Efficacy and safety of intravenous and oral Nadolol for supraventricular tachycardia in children
Journal of the American College of Cardiology, 1992Co-Authors: Ashok V. Mehta, Balasubrahmanyam ChidambaramAbstract:The efficacy and safety of oral Nadolol in supraventricular tachycardia were evaluated prospectively in 27 children (median age 5.5 years). Fifteen patients had an unsuccessful trial of digoxin therapy. Intravenous Nadolol was given to seven patients during electrophysiologic study; five of these had an excellent response and two had a partial response (25% decrease in tachycardia rate). Six of these patients had a similar response to oral Nadolol. Twelve patients received both propranolol and Nadolol. Among six patients, intravenous propranolol was successful in four and unsuccessful in two; all six had a similar response to oral Nadolol. With oral propranolol, tachycardia was well controlled in four patients and persistent in two; five of five patients had a similar response to oral Nadolol. Twenty-six patients were treated with oral Nadolol; the ar- rhythmia was well controlled in 23, 2 had recurrent tachycardia and 1 patient had tachycardia at a 25% slower rate. The effective dose of Nadolol ranged between 0.5 and 2.5 mg/kg body weight once daily (median dose 1 mg/kg per day). During follow-up (3 to 36 months), compliance and tolerance were excellent; excluding 2 patients with reactive airway disease who developed wheezing, only 3 (12%) of 24 had side effects necessitating a change in drug therapy. Once a day Nadolol is a safe and effective agent in the management of supraventricular tachycardia in children. Its long-term efficacy can be predicted by the short-term response to intravenous Nadolol or propranolol during programmed electrophysiologic study.
-
Pharmacokinetics of Nadolol in children with supraventricular tachycardia.
Journal of clinical pharmacology, 1992Co-Authors: Ashok V. Mehta, Balasubrahmanyam Chidambaram, Peter J. RiceAbstract:The pharmacokinetics of intravenous and oral Nadolol, a long-acting beta-adrenoceptor blocking agent, were investigated in six children receiving the drug for treatment of supraventricular tachycardia. In the youngest patient (age 3 months), no distribution phase was seen. In children younger than 22 months of age, Nadolol is more rapidly eliminated (t1/2 = 4.3 hours or less) than in older children, in whom elimination is more similar to that in adults (t1/2 approximately 7.3-15.7 hours). After intravenous administration, Nadolol displayed two-compartment pharmacokinetics with a distribution phase (t1/2 = 0.2-1.1 hours) followed by elimination. Large changes in Nadolol pharmacokinetics may occur during the first year of life. Nadolol should be used cautiously in infants.
R. Marin - One of the best experts on this subject based on the ideXlab platform.
-
long term results of a clinical trial of Nadolol with or without isosorbide mononitrate for primary prophylaxis of variceal bleeding in cirrhosis
Hepatology, 2000Co-Authors: Carlo Merkel, Carole Donada, Giorgio Cavallarin, Pierluigi Torboli, Giuliana Sebastianelli, Massimo Bolognesi, R. Marin, Piero Amodio, David Sacerdoti, Martina FelderAbstract:It is clearly established that β-blockers decrease the risk of a first variceal bleeding in cirrhosis. We have recently shown that the addition of isosorbide mononitrate to Nadolol decreases the rate of variceal bleeding in patients with cirrhosis and varices, compared with Nadolol alone, after a median follow-up of 30 months. It is not established if the long-term treatment with the combination continues to be beneficial. Therefore, we assessed the long-term effect of this combination on first variceal bleeding, complications, and death. One hundred forty-six cirrhotic patients with esophageal varices included in a previously published multicenter, randomized study comparing Nadolol (40-160 mg/d) with the combination Nadolol plus isosorbide mononitrate (10-20 mg 3 times per day) were followed up for up to 7 years (median follow-up, 55 months). The primary end-point was variceal bleeding of any severity. Twenty-four patients (16 in the Nadolol group, and 8 in the combination group) experienced variceal bleeding (log rank test, P = .02). Cumulative risk of bleeding was 29% and 12%, respectively (95% CI for the difference, 1%-23%). Two and 4 patients, respectively, had bleeding from portal hypertensive gastropathy (log rank test, P = .20). Thirty and 25 patients, respectively, died during follow-up (log rank test, P = .13). Twelve and 10 patients, respectively, had de novo occurrence of ascites during follow-up (log rank test, P = .29). In conclusion, Nadolol plus isosorbide mononitrate is significantly more effective than Nadolol alone in the long-term use. Side effects are few, and no deleterious effects on ascites occurrence or on survival occur after long-term use of this combination.
-
long term results of a clinical trial of Nadolol with or without isosorbide mononitrate for primary prophylaxis of variceal bleeding in cirrhosis
Hepatology, 2000Co-Authors: Carlo Merkel, Carole Donada, Giorgio Cavallarin, Pierluigi Torboli, Giuliana Sebastianelli, Massimo Bolognesi, R. Marin, Piero Amodio, David Sacerdoti, Martina FelderAbstract:It is clearly established that beta-blockers decrease the risk of a first variceal bleeding in cirrhosis. We have recently shown that the addition of isosorbide mononitrate to Nadolol decreases the rate of variceal bleeding in patients with cirrhosis and varices, compared with Nadolol alone, after a median follow-up of 30 months. It is not established if the long-term treatment with the combination continues to be beneficial. Therefore, we assessed the long-term effect of this combination on first variceal bleeding, complications, and death. One hundred forty-six cirrhotic patients with esophageal varices included in a previously published multicenter, randomized study comparing Nadolol (40-160 mg/d) with the combination Nadolol plus isosorbide mononitrate (10-20 mg 3 times per day) were followed up for up to 7 years (median follow-up, 55 months). The primary end-point was variceal bleeding of any severity. Twenty-four patients (16 in the Nadolol group, and 8 in the combination group) experienced variceal bleeding (log rank test, P =.02). Cumulative risk of bleeding was 29% and 12%, respectively (95% CI for the difference, 1%-23%). Two and 4 patients, respectively, had bleeding from portal hypertensive gastropathy (log rank test, P =.20). Thirty and 25 patients, respectively, died during follow-up (log rank test, P =.13). Twelve and 10 patients, respectively, had de novo occurrence of ascites during follow-up (log rank test, P =.29). In conclusion, Nadolol plus isosorbide mononitrate is significantly more effective than Nadolol alone in the long-term use. Side effects are few, and no deleterious effects on ascites occurrence or on survival occur after long-term use of this combination.
-
hemodynamic evaluation of the addition of isosorbide 5 mononitrate to Nadolol in cirrhotic patients with insufficient response to the beta blocker alone
Hepatology, 1997Co-Authors: Carlo Merkel, E Enzo, Massimo Bolognesi, R. Marin, David Sacerdoti, Giancarlo Bombonato, Paolo Angeli, Angelo GattaAbstract:The association beta-blockers plus isosorbide-5-mononitrate (I5M) has been proposed for the treatment of portal hypertension in patients with insufficient response to beta-blockers alone, according to hemodynamic criteria. The mechanism of action in these patients is not clearly defined. Fifteen patients with cirrhosis and esophageal varices were evaluated by hepatic venous pressure gradient (HVPG) measurement and duplex-Doppler ultrasonography before and after 1 month of treatment with Nadolol. Nine patients who did not exhibit a decrease in HVPG to 12 mm Hg or a percent decrease greater than 20% were classified as poor responders, and were studied again with the same methodology after 3 months of chronic administration of Nadolol + I5M 20 mg twice per day. In poor responders, mean HVPG decrease after Nadolol was 8.9% +/- 2.8%, and after the combination, it was 25.7% +/- 1.7% (P = .004). All patients except one became good responders to the association. Portal blood flow (PBF) decreased significantly after Nadolol (P = .004), and remained unchanged after the addition of nitrates. Resistance to portal blood flow (RPBF) increased after Nadolol (P = .02) and returned to baseline values during combined treatment (P = .03). In good responders, an adequate decrease in HVPG was associated with a decrease in PBF (P = .06) but no change in RPBF. A wide spectrum of combined changes in PBF and in RPBF after Nadolol was observed in poor responders, ranging from no change in either parameter to a marked decrease in PBF counterbalanced by a marked increase in RPBF. The addition of I5M was followed in most cases by larger effects on resistance than on flow. Doppler parameters were not significantly correlated with the HVPG response to Nadolol alone or associated with I5M. It is concluded that good hemodynamic responders to Nadolol differ from poor responders in the lack of increase in RPBF after the drug. The addition of nitrates to Nadolol is effective in decreasing portal pressure in most poor responders to Nadolol alone. A decrease in outflow resistance is the main mechanism involved.
-
randomised trial of Nadolol alone or with isosorbide mononitrate for primary prophylaxis of variceal bleeding in cirrhosis
The Lancet, 1996Co-Authors: Carlo Merkel, E Enzo, Carole Donada, Giorgio Cavallarin, Pierluigi Torboli, Giuliana Sebastianelli, R. Marin, Piero Amodio, David Sacerdoti, Martina FelderAbstract:Summary Background The risk of having a first cirrhosis-associated variceal bleed is lowered by about 50% by β-blockers. Use of β-blockers is currently recommended for patients with cirrhosis and oesophageal varices that are at risk of bleeding. We aimed to test the effectiveness of isosorbide mononitrate as an adjunct to the β-blocker Nadolol in the prophylaxis of first variceal bleeding in these patients. Methods We did a randomised multicentre study to compare the non-selective β -blocker, Nadolol, with Nadolol plus isosorbide mononitrate in 146 relatively well (Child-Pugh score ≤11) patients who had oesophageal varices at risk of bleeding. Patients on Nadolol alone received a single oral 40 mg daily dose. Every second day the dose was titrated to achieve 20–25% decrease in resting heart rate (maximum dose 160 mg daily). Patients receiving both drugs received Nadolol as above then isosorbide mononitrate was added starting with 10 mg orally twice daily, which was increased to 20 mg unless hypotension or severe headache occurred. The main endpoint was the occurrence of variceal bleeding of any severity. Patients were followed up for up to 40 months. Findings During the study period 11 of 74 patients from the Nadolol alone group and four of 72 from the nadalol plus isosorbide mononitrate group had variceal bleeding (logrank test p=0·03). Cumulative risk of variceal bleeding was 18% in the Nadolol group and 7·5% in the combined treatment group (95% CI for difference 1–25%). Two patients in each group had a non-variceal bleed related to portal hypertension. 14 patients from the Nadolol only group and eight from the combined treatment group died during the study period (log-rank test p=0·09). Four and eight patients, respectively, had to discontinue one of the drugs because of side-effects. Interpretation Nadolol plus isosorbide mononitrate is signifcantly more effective than Nadolol alone in the primary prophylaxis of variceal bleeding in relatively well patients with cirrhosis, and has few side-effects.