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British Journal of Clinical Pharmacology Apr 1994Duplex scanning was used to measure liver blood flow (hepatic artery and main branches of the portal and hepatic veins) in six healthy subjects, five cirrhotic patients,... (Comparative Study)
Comparative Study
Duplex scanning was used to measure liver blood flow (hepatic artery and main branches of the portal and hepatic veins) in six healthy subjects, five cirrhotic patients, and six hepatitis patients. Antipyrine clearance and formation clearances to its metabolites were also measured. Compared with healthy control subjects, cirrhotic patients had a lower hepatic vein blood flow (-76%, P < 0.05). This was due primarily to a lower portal vein blood flow (-36%, NS). A statistically significant difference in liver blood flow between patients with hepatitis and normal subjects was not detected. Antipyrine half-life, clearance, and the area under the serum drug concentration vs time curve were significantly different in cirrhotic patients compared with the healthy subjects (mean +/- s.d.-healthy controls: t1/2 = 13.7 +/- 3.0 h, CL = 30.0 +/- 8.6 ml h-1 kg-1, AUC = 549 +/- 139 mg l-1 h; cirrhotic patients: t1/2 = 32.4 +/- 1.7 h, CL = 12.3 +/- 2.1 ml h-1 kg-1, AUC = 1061 +/- 218 mg l-1 h; P < 0.008). Antipyrine half-life, clearance, and the area under the serum drug concentration vs time curve were not significantly different in hepatitis patients compared with the healthy subjects (hepatitis patients: t1/2 = 14.3 +/- 3.7 h, CL = 29.3 +/- 8.5 ml h-1 kg-1, AUC = 498 +/- 142 mg l-1 h). The volume of distribution of antipyrine was similar in all three groups of subjects.(ABSTRACT TRUNCATED AT 250 WORDS)
Topics: Adult; Antipyrine; Female; Half-Life; Hepatitis B; Hepatitis C; Hepatitis, Chronic; Humans; Liver Circulation; Liver Cirrhosis, Alcoholic; Male; Metabolic Clearance Rate; Middle Aged
PubMed: 8018459
DOI: 10.1111/j.1365-2125.1994.tb04292.x -
Therapeutic Advances in Cardiovascular... Aug 2016In the present study, we investigated whether combination therapy of low-dose benidipine with the potent free radical scavenger edaravone has a cardioprotective effect...
Edaravone, a potent free radical scavenger and a calcium channel blocker attenuate isoproterenol induced myocardial infarction by suppressing oxidative stress, apoptotic signaling and ultrastructural damage.
OBJECTIVES
In the present study, we investigated whether combination therapy of low-dose benidipine with the potent free radical scavenger edaravone has a cardioprotective effect against isoproterenol (ISO)-induced myocardial infarction (MI) in Wistar rats.
METHODS
Rats were pretreated with concurrent doses of benidipine and edaravone (1 μg/kg/day + 1 mg/kg/day and 3 μg/kg/day + 3 mg/kg/day) by intravenous (i.v.) and intraperitoneal (i.p.) routes respectively for 28 days, followed by MI induction using ISO (85 mg/kg) by subcutaneous route for two days at 24 h intervals. After the treatment period, blood was withdrawn and the heart was preserved for biochemical estimations.
RESULTS
The activities of the cardiac biomarkers (lactate dehydrogenase and creatine kinase-MB), and the level of malondialdehyde (MDA) significantly increased, while antioxidant markers (reduced glutathione, catalase, superoxidase dismutase, glutathione peroxidase, glutathione reductase) were significantly decreased in the ISO intoxicated group compared with the control group. Moreover, the level of C-reactive protein (CRP) and Caspase-3 activity significantly increased in ISO-intoxicated group. An ultrastructure study was also carried out. Pretreatment with a combination of benidipine and edaravone significantly attenuated the activities of the cardiac biomarkers and the level of MDA, and significantly increased the antioxidant markers compared with the ISO-intoxicated group. Furthermore, pretreatment with the combination of benidipine and edaravone significantly decreased the level of CRP and Caspase-3 activity as compared to the ISO-treated group. The ultrastructure study of myocardium revealed that pretreated groups preserved the mitochondrial shape, the membrane and its internal structures.
CONCLUSION
Taken together these results suggest that the combination of benidipine and edaravone showed significant protective effect in ISO-induced MI.
Topics: Animals; Antipyrine; Apoptosis; C-Reactive Protein; Calcium Channel Blockers; Caspase 3; Dihydropyridines; Edaravone; Female; Free Radical Scavengers; Isoproterenol; Male; Malondialdehyde; Myocardial Infarction; Myocardium; Oxidative Stress; Rats; Rats, Wistar
PubMed: 26868288
DOI: 10.1177/1753944716630653 -
Chemosphere Nov 2023In recent years, heterogeneous electro-Fenton processes have gained considerable attention as an alternative to homogeneous processes. In this context, the aim of this...
In recent years, heterogeneous electro-Fenton processes have gained considerable attention as an alternative to homogeneous processes. In this context, the aim of this study is the use of a commercial iron metal-organic framework (Fe-MOF), Basolite® F-300, as a base material for the design of a heterogeneous electro-Fenton treatment system for the removal of antipyrine. Initially, the catalyst was applied as powder in aqueous solution and three key parameters of the electro-Fenton process (pH, Fe-MOF concentration and current density) were evaluated and optimized by a Central Composite Design Face Centred (CCD-FC) using antipyrine removal and energy consumption as response functions. Near complete antipyrine removal (94%) was achieved under optimal conditions: pH 3, Fe-MOF 157.78 mg/L and current density 6.67 mA/cm, obtaining an energy consumption of 0.29 W·h per mg of antipyrine removed. Later, two electrocatalysts (Fe-MOF functionalized cathodes), prepared by different Fe-MOF immobilisation approaches (composite of carbon black/polytetrafluoroethylene or by electrospinning on Ni foam), were synthesized. Their characterisation showed notable Fe-MOF incorporation into the material and favourable properties as electrocatalysts. Both Fe-MOF functionalized cathodes were evaluated in the removal of antipyrine at different pH (acidic and natural) and current density (27.78 and 55.56 mA/cm), achieving in the best conditions removal levels around 80% in 1 h without any operational problems. In addition, several intermediates generated during the treatment were identified and their toxicity estimated. According to the obtained results, the degradation compounds have less toxicity than the parent compounds, confirming the effectiveness of the treatment.
Topics: Antipyrine; Electrodes; Iron; Metal-Organic Frameworks; Powders
PubMed: 37634590
DOI: 10.1016/j.chemosphere.2023.139942 -
British Journal of Clinical Pharmacology Jul 19871 Oxidative metabolism of antipyrine (AP) was compared in 11 elderly (greater than 65 years) and 12 young (less than 40 years) volunteers. All subjects were non-smokers,... (Comparative Study)
Comparative Study
1 Oxidative metabolism of antipyrine (AP) was compared in 11 elderly (greater than 65 years) and 12 young (less than 40 years) volunteers. All subjects were non-smokers, consumed little if any alcohol and were in good health. 2 After a single dose of AP 500 mg, its clearance from saliva and profiles of the parent drug and its major metabolites in urine were determined using high-performance liquid chromatography. 3 Mean total AP clearance from saliva was lower in the elderly (P less than 0.05). Mean weight-normalised volume of distribution was also smaller (P less than 0.01) so that elimination half-life in the elderly was not significantly different from that in the young. 4 The percentage dose excreted in 48 h urine as norantipyrine (NORA) and its clearance for production were lower in the elderly (P less than 0.001 and P less than 0.01 respectively). Urinary 3-hydroxymethylantipyrine (HMA) and free antipyrine were present in greater quantities in 48 h urine in the elderly (P less than 0.001 and P less than 0.05) while the amounts of 4-hydroxyantipyrine (OHA) were almost identical in the two age groups. 5 The findings suggest that there is a selective impairment of N-demethylation in the elderly which may have important implications for dosage of elderly patients with drugs metabolised by this route.
Topics: Adult; Aged; Aging; Antipyrine; Biotransformation; Female; Half-Life; Humans; Kinetics; Male; Saliva
PubMed: 3620285
DOI: 10.1111/j.1365-2125.1987.tb03135.x -
British Journal of Clinical Pharmacology Nov 1998To determine whether lean body mass (LBM), a possible surrogate of liver and kidney volumes, correlates with hepatic and renal drug clearances.
AIMS
To determine whether lean body mass (LBM), a possible surrogate of liver and kidney volumes, correlates with hepatic and renal drug clearances.
METHODS
Twenty-one disease-free patients with a history of cancer and with normal hepatic and renal function were studied. Salivary pharmacokinetics of oral antipyrine (1200 mg) and 24 h creatinine clearance were determined following the determination of LBM by dual energy X-ray absorptiometry and the determination of liver and kidney volumes by helical CT scanning.
RESULTS
Liver volume correlated with LBM (r2=0.21, P=0.04), body surface area (BSA) (r2=0.54, P<0.001), and total body weight (TBW) (r2=0.61, P<0.001). Kidney volume correlated with LBM (r2=0.49, P<0.001), BSA (r2=0.43, P=0.002) and TBW (r2=0.24, P=0.03). Stepwise multiple regression analysis, incorporating the independent variables of age, height, weight, sex, BSA, LBM, alcohol consumption, smoking status and liver volume and the dependent variable antipyrine clearance, indicated that LBM was the only independent correlate of antipyrine clearance. A stepwise multiple regression analysis with kidney volume in the independent variables, and creatinine clearance as dependent variable, showed that kidney volume and age were the only independent correlates of creatinine clearance. A nomogram using serum creatinine and LBM was comparable with the Cockcroft and Gault nomogram in calculating creatinine clearance.
CONCLUSIONS
Of the anthropometric variables tested, LBM was the only determinant of antipyrine clearance, but this was not due to a relationship between LBM and liver volume. By contrast, the relationship between creatinine clearance and LBM appeared to be due to a relationship between LBM and kidney volume.
Topics: Adult; Aged; Antipyrine; Body Weight; Creatine; Female; Humans; Kidney; Kidney Function Tests; Liver; Liver Function Tests; Male; Metabolic Clearance Rate; Middle Aged
PubMed: 9833597
DOI: 10.1046/j.1365-2125.1998.00812.x -
British Journal of Clinical Pharmacology Nov 1984The effect of liver cirrhosis on plasma clearance and metabolite profile of i.v. administered antipyrine was studied in 23 patients with alcoholic liver cirrhosis (age...
The effect of liver cirrhosis on plasma clearance and metabolite profile of i.v. administered antipyrine was studied in 23 patients with alcoholic liver cirrhosis (age 37-70 years) and 17 healthy subjects (age 28-55 years). Liver volume was also measured and was found to be larger in patients than in controls, mean values being 1.86 and 1.36 l respectively. The elimination half-life of antipyrine in patients with alcoholic liver cirrhosis was significantly longer than in the healthy subjects (P less than 0.001). Mean values were 39.9 and 10.1 h respectively. Alcoholic liver cirrhosis had no effect on the apparent volume of distribution of antipyrine, but antipyrine plasma clearance was substantially reduced in the patients. Mean clearance values (ranges) were 13.5 (9.3-22.8) ml/min in the patients and 49.3 (31.1-103) ml/min in healthy subjects. Normalization of antipyrine plasma clearance for liver volume resulted in an only slightly increased distinction between patients and healthy subjects, mean values (ranges) being 7.8 (3.3-13.0) ml min(-1) 1(-1) and 36.1 (21.9-35.9) ml min(-1) 1(-1) respectively. The cumulative renal excretion of 4-hydroxyantipyrine (OHA) and norantipyrine (NORA) was significantly lower in patients with alcoholic liver cirrhosis than in healthy subjects, as was the total recovery of antipyrine and major metabolites from urine. Mean values were 15.0, 8.4 and 41.2% of dose in the patients respectively and 24.3, 25.8 and 68.9% of dose in the control subjects. Excreted amounts of total and unconjugated 3-hydroxymethylantipyrine (HMA) and of unchanged antipyrine were the same in the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Topics: Adult; Aged; Antipyrine; Glucuronates; Humans; Liver Cirrhosis, Alcoholic; Metabolic Clearance Rate; Middle Aged
PubMed: 6508980
DOI: 10.1111/j.1365-2125.1984.tb02533.x -
Arthritis and Rheumatism Oct 2011Patients with systemic sclerosis (SSc) exhibit enhanced production of free radicals due to ischemia and reperfusion injury following Raynaud's phenomenon, an initial...
OBJECTIVE
Patients with systemic sclerosis (SSc) exhibit enhanced production of free radicals due to ischemia and reperfusion injury following Raynaud's phenomenon, an initial clinical manifestation. Oxidative stress induces cytokine production, inflammatory cell recruitment, and tissue injury in several inflammatory diseases. The aim of this study was to examine the effect of edaravone, a free radical scavenger, on the development of fibrosis and autoimmunity in two different mouse models of SSc.
METHODS
The bleomycin-induced SSc model in mice and the tight skin mouse model were used to evaluate the effect of edaravone on fibrosis and immunologic abnormalities. To assess the reaction of fibroblasts to stimulation with free radicals, fibroblasts from these mice were cultured with NONOate, a nitric oxide-releasing agent, and hydrogen peroxide.
RESULTS
Treatment with edaravone reduced fibrosis in mice with bleomycin-induced SSc and in TSK/+ mice. The production of free radicals was also attenuated by edaravone in both models. In addition, production of fibrogenic cytokines such as interleukin-6 and transforming growth factor β1, production of anti-topoisomerase I antibody, and the degree of hypergammaglobulinemia were reduced by edaravone. Furthermore, bleomycin induced the production of H2O2 and nitric oxide from inflammatory cells, and collagen production was increased in fibroblasts cultured with H2O2 and NONOate.
CONCLUSION
This study is the first to show that edaravone has a significant inhibitory effect on fibrosis both in the bleomycin-induced SSc model and in TSK/+ mice. These results indicate that edaravone should be further evaluated for potential use as an antifibrotic agent in SSc.
Topics: Animals; Antipyrine; Bleomycin; Disease Models, Animal; Edaravone; Fibrosis; Free Radical Scavengers; Mice; Pulmonary Fibrosis; Scleroderma, Systemic; Skin; Treatment Outcome
PubMed: 21618208
DOI: 10.1002/art.30470 -
BMC Neurology Jul 2022Amyotrophic lateral sclerosis (ALS) is a lethal neurodegenerative disease characterized by the gradual loss of upper and lower motor neurons that leads to progressive... (Observational Study)
Observational Study
BACKGROUND
Amyotrophic lateral sclerosis (ALS) is a lethal neurodegenerative disease characterized by the gradual loss of upper and lower motor neurons that leads to progressive muscle atrophy and weakness. Edaravone, a free-radical scavenger, was approved as an ALS treatment in 2015 in South Korea.
METHODS
This study investigated the long-term effects and safety of edaravone by reviewing the medical records of 16 Korean patients with ALS who received extended edaravone between 2015 and 2021 in a single tertiary ALS center.
RESULTS
Among sixteen patients, eleven patients underwent extended edaravone therapy for more than 18 cycles (72 weeks). The mean monthly changes in the revised ALS Functional Rating Scale (ALSFRS-R) were - 0.96 ± 0.83 (0-24 weeks), - 0.70 ± 0.76 (24-48 weeks), - 1.18 ± 1.67 (48-72 weeks), and - 0.81 ± 0.60 (0-72 weeks). The mean decline in forced vital capacity (FVC) was 17.4 ± 24.1. The changes were significant in both ALSFRS-R (p < 0.001) and FVC (p = 0.048); however, the mean change in compound muscle action potential of phrenic nerves was not. Patients experienced only minor adverse events, which were well tolerated.
CONCLUSIONS
This study verifies previous reported outcomes of edaravone in 16 Korean ALS patients, indicating a modest effect with a favorable safety profile.
Topics: Amyotrophic Lateral Sclerosis; Antipyrine; Double-Blind Method; Edaravone; Humans; Neurodegenerative Diseases; Republic of Korea
PubMed: 35836136
DOI: 10.1186/s12883-022-02788-x -
British Journal of Clinical Pharmacology Mar 19821 Effects of rifampicin on the pharmacokinetics of single oral doses of metoprolol and antipyrine are reported. 2 Rifampicin, administered daily for 15 days, reduced the...
1 Effects of rifampicin on the pharmacokinetics of single oral doses of metoprolol and antipyrine are reported. 2 Rifampicin, administered daily for 15 days, reduced the area under the plasma concentration-time curve (AUC) of metoprolol but the rate constant for elimination (beta) of metoprolol from plasma did not alter significantly. 3 Administration of rifampicin for 13 days reduced AUC and increased beta of antipyrine. Thirteen days after discontinuing rifampicin. AUC and beta of antipyrine remained significantly different from the initial values. 4 Some loss of beta-adrenoceptor blockade should be anticipated if rifampicin is administered to patients who are receiving metoprolol.
Topics: Adult; Antipyrine; Drug Interactions; Humans; Kinetics; Male; Metoprolol; Propanolamines; Rifampin
PubMed: 7059439
DOI: 10.1111/j.1365-2125.1982.tb01390.x -
Methods in Molecular Biology (Clifton,... 2016The rate of blood flow through a tissue (F) is a critical parameter for assessing the functional efficiency of a blood vessel network following angiogenesis. This...
The rate of blood flow through a tissue (F) is a critical parameter for assessing the functional efficiency of a blood vessel network following angiogenesis. This chapter aims to provide the principles behind the estimation of F, how F relates to other commonly used measures of tissue perfusion, and a practical approach for estimating F in laboratory animals, using small readily diffusible and metabolically inert radio-tracers. The methods described require relatively nonspecialized equipment. However, the analytical descriptions apply equally to complementary techniques involving more sophisticated noninvasive imaging.Two techniques are described for the quantitative estimation of F based on measuring the rate of tissue uptake following intravenous administration of radioactive iodo-antipyrine (or other suitable tracer). The Tissue Equilibration Technique is the classical approach and the Indicator Fractionation Technique, which is simpler to perform, is a practical alternative in many cases. The experimental procedures and analytical methods for both techniques are given, as well as guidelines for choosing the most appropriate method.
Topics: Animals; Antipyrine; Biological Assay; Blood Circulation; Blood Flow Velocity; Intravital Microscopy; Mice; Neovascularization, Physiologic; Tissue Culture Techniques
PubMed: 27172960
DOI: 10.1007/978-1-4939-3628-1_18