The present study describes a simple, reliable and reproducible liquid chromatography–tandem mass spectrometry method(LC–MS/MS) for the simultaneous determination of allopurinol and its active metabolite,oxypurinol ...The present study describes a simple, reliable and reproducible liquid chromatography–tandem mass spectrometry method(LC–MS/MS) for the simultaneous determination of allopurinol and its active metabolite,oxypurinol in human plasma for a pharmacokinetic/bioequivalence study. After protein precipitation(PPT) of100 μL plasma sample with 1.0% formic acid in acetonitrile, the recovery of the analytes and allopurinol-d2 as an internal standard ranged from 85.36% to 91.20%. The analytes were separated on Hypersil Gold(150 mm×4.6 mm, 5 μm) column using 0.1% formic acid-acetonitrile(98:2, v/v) as the mobile phase.Quantification was done using electrospray ionization in the positive mode. The calibration concentration range was established from 60.0 to 6000 ng/m L for allopurinol and 80.0–8000 ng/m L for oxypurinol. Matrix effect in human plasma, expressed as IS-normalized matrix factors ranged from 1.003 to 1.030 for both the analytes. The developed method was found suitable for a clinical study with 300 mg allopurinol tablet formulation in healthy subjects.展开更多
Free radicals in ischemic and reperfused rat brain were measured by electron spinresonance(ESR) spectrometer.The inhibitory effect of allopurinol on the free radical genera-tion in reperfused rat brain was observed.Th...Free radicals in ischemic and reperfused rat brain were measured by electron spinresonance(ESR) spectrometer.The inhibitory effect of allopurinol on the free radical genera-tion in reperfused rat brain was observed.The experimental results revealed that the free radi-cal content of the brain in the ischemia group was markedly higher than that in the control group(P【0.01),that in the reperfusion group was markedly higher than that in the ischemia group(P【0.01)and that in the allopurinol group was markedly lower than that in the reperfusiongroup(P【0.01).These results suggest that free radicals increase.greatly after cerebralischemia-reperfusion and that allopurinol plays a certain inhibitory role in the free radical genera-tion in the reperfused rat brain.展开更多
Over the last 20 years, it has emerged that, while surgical revascularisation of extensive ischaemic heart disease may have prognostic advantages, the main issues considered regarding individual management are usually...Over the last 20 years, it has emerged that, while surgical revascularisation of extensive ischaemic heart disease may have prognostic advantages, the main issues considered regarding individual management are usually those of symptomatic improvement only. The major impetus towards invasive intervention is therefore failure of prophylactic anti-anginal therapy. On the other hand, many patients, especially the elderly, now present the clinical problem of ongoing angina without residual invasive options. There is an ongoing need for more effective anti-anginal therapies. Of the currently available major classes of prophylactic anti-anginal agents, neither nitrates, β-blockers nor calcium antagonists generally produce marked improvements in exercise duration. Three areas of new therapeutic development in anti-anginal therapy are worthy of note. These involve the sinus node inhibitor ivabradine, high dose allopurinol (xanthine oxidase inhibitor) and a new class of “metabolic modulators” represented by perhexiline, trimetazidine and probably ranolazine. The current review addresses the therapeutic potential of these agents. Notably, all of these “new” drugs are potentially suitable for management of angina in the setting of impaired left ventricular systolic function, and they may also be utilized in patients with angina independent of the presence of coronary disease (for example in hypertrophic cardiomyopathy). The current evidence for efficacy and potential future development in this area are reviewed.展开更多
Oral dissolving gelatin beads (GBs) containing allopurinol (AP) were prepared by the seamless capsule method and their rheological properties were examined. The release profiles of both gelatin and AP from GBs were al...Oral dissolving gelatin beads (GBs) containing allopurinol (AP) were prepared by the seamless capsule method and their rheological properties were examined. The release profiles of both gelatin and AP from GBs were also investigated in limited dissolution medium. GBs containing AP provided an easy-to-handle dosage form, but the physical strength of the beads immediately decreased upon contact with physiological saline at 37℃. Gelatin was released from the outer layer of GBs in physiological saline, with almost all the gelatin dissolved after 5 min, together with approximately 30% of the AP contained in the inner layer of the GB. The oral administration of GBs likely results in immediate softening of the GB upon contact with saliva. The released AP acts directly at inflammation sites, in a manner similar following oral rinsing with an AP suspension. Therefore, GBs are a useful dosage form for preventing or treating localized problems in the oral cavity, such as mucositis.展开更多
Introduction: The Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) syndrome is a very rare iatrogenic accident that is characterized by its difficult diagnosis due to its clinical latency and heterogeneous cl...Introduction: The Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) syndrome is a very rare iatrogenic accident that is characterized by its difficult diagnosis due to its clinical latency and heterogeneous clinic. The form induced by allopurinol remains exceptional and often ignored by clinicians, although potentially fatal. We are reporting an original observation of allopurinol-induced DRESS syndrome in elderly. Case report: A 64-year-old woman who had been treated with allopurinol for gout for three weeks, was hospitalized for a diffuse, erythematous and maculopapular cutaneous rash, associated with fever at 39℃ , dyspnea, generalized lymphadenopathy, and a hyperkeratotic and desquamative plantar eruption. The biology showed eosinophilia at 860/mm3 and cytolitic hepatitis without cholestasis or hepatocellular insufficiency with ASAT at 230 IU/l and alanine aminotransferase ( ALAT) at 280 IU/l. The infectious, immunological investigation, as well as the search for underlying malignant neoplasia or hematological malignancy were negative. The skin biopsy was inconclusive. The diagnosis of a DRESS syndrome induced by allopurinol was retained. The evolution was rapidly favorable after stopping allopurinol and treatment with systemic glucocorticoids. Conclusion: The incidence of cutaneous reactions to allopurinol is estimated at 1.5/100,000 H/year. The DRESS syndrome, the most serious form of these reactions, remains exceptional. This particular form of toxicity deserves to be known by clinicians, especially since allopurinol is widely prescribed in the elderly.展开更多
AIM: To determine the effects of allopurinol, an inhibitor of xanthine oxidase, and apocynin, an inhibitor of NADPH oxidase, on oxidant stress and liver injury caused by hepatic ischemia/reperfusion (I/R) procedure in...AIM: To determine the effects of allopurinol, an inhibitor of xanthine oxidase, and apocynin, an inhibitor of NADPH oxidase, on oxidant stress and liver injury caused by hepatic ischemia/reperfusion (I/R) procedure in mice. METHODS: Mice were pretreated with a xanthine oxidase inhibitor, allopurinol, or NADPH oxidase (NOX) inhibitor, apocynin before the hepatic I/R procedure. Then treated or untreated mice underwent the hepatic I/R procedure. The effects on hepatic injury and superoxide anions were determined after starting reperfusion. RESULTS: A standard warm hepatic I/R procedure led to a marked increase in superoxide anion production as indicated by a superoxide anion tracer, MCLA. At the same time, the procedure caused profound acute liver injury, as indicated by elevated serum alanine aminotransferase and tumor necrosis factor-α levels, reduced liver glutathione levels and elevated malondialdehyde contents, as well as a high apoptotic cell count. All these changes were reversed by the use of apocynin or allopurinol prior to the hepatic I/R procedure. CONCLUSION: Allopurinol and apocynin exerted protective effects on hepatic ischemia/reperfusion injury. The protection is associated with blocking the generationof superoxide anions during the hepatic I/R procedure by inhibiting xanthine oxidase and NADPH oxidase activity.展开更多
OBJECTIVE:To evaluate the effect of Dahuang Mudan Tang(大黄牡丹汤,DHMD)and allopurinol on the treatment of chronic kidney disease staged G1-G3b patients with hyperuricemia and to provide novel insights into the clinic...OBJECTIVE:To evaluate the effect of Dahuang Mudan Tang(大黄牡丹汤,DHMD)and allopurinol on the treatment of chronic kidney disease staged G1-G3b patients with hyperuricemia and to provide novel insights into the clinical management of chronic kidney disease complications.METHODS:A total of 80 chronic kidney patients staged G1-G3b with hyperuricemia were randomly grouped to receive single allopurinol treatment(control)and combined treatment with DHMD(treated)for 8 weeks.The kidney function and proteinuria indicators of patients were compared between pre-and post-treatment.The oxidative stress and inflammation responses were evaluated by corresponding indicators and cytokines.The clinical efficiency rate and adverse reaction events were also summarized to assess the therapeutic efficiency and safety.RESULTS:The kidney function and proteinuria of enrolled patients were alleviated after their therapies,behaved as the increasing estimated glomerular filtration rate and decreasing serum creatinine,serum uric acid,urea nitrogen,24 h urine protein levels.On the other hand,the malondialdehyde level and pro-inflammation cytokines were suppressed by the therapies,and the superoxide dismutase was found to be significantly enhanced.Patients in the treated groups showed a better recovery in kidney function,proteinuria,oxidative stress,and inflammation response.Moreover,patients in the treated group showed a higher efficiency rate(95%)and fewer adverse reaction events(5%).CONCLUSIONS:The combination of allopurinol with DHMD significantly promoted the recovery of chronic kidney disease stage G1-G3b patients with hyperuricemia,which can be considered a novel clinical therapeutic strategy.展开更多
基金the support and necessary facilities provided by Accutest Research Lab, Ahmedabad, for this work
文摘The present study describes a simple, reliable and reproducible liquid chromatography–tandem mass spectrometry method(LC–MS/MS) for the simultaneous determination of allopurinol and its active metabolite,oxypurinol in human plasma for a pharmacokinetic/bioequivalence study. After protein precipitation(PPT) of100 μL plasma sample with 1.0% formic acid in acetonitrile, the recovery of the analytes and allopurinol-d2 as an internal standard ranged from 85.36% to 91.20%. The analytes were separated on Hypersil Gold(150 mm×4.6 mm, 5 μm) column using 0.1% formic acid-acetonitrile(98:2, v/v) as the mobile phase.Quantification was done using electrospray ionization in the positive mode. The calibration concentration range was established from 60.0 to 6000 ng/m L for allopurinol and 80.0–8000 ng/m L for oxypurinol. Matrix effect in human plasma, expressed as IS-normalized matrix factors ranged from 1.003 to 1.030 for both the analytes. The developed method was found suitable for a clinical study with 300 mg allopurinol tablet formulation in healthy subjects.
文摘Free radicals in ischemic and reperfused rat brain were measured by electron spinresonance(ESR) spectrometer.The inhibitory effect of allopurinol on the free radical genera-tion in reperfused rat brain was observed.The experimental results revealed that the free radi-cal content of the brain in the ischemia group was markedly higher than that in the control group(P【0.01),that in the reperfusion group was markedly higher than that in the ischemia group(P【0.01)and that in the allopurinol group was markedly lower than that in the reperfusiongroup(P【0.01).These results suggest that free radicals increase.greatly after cerebralischemia-reperfusion and that allopurinol plays a certain inhibitory role in the free radical genera-tion in the reperfused rat brain.
文摘Over the last 20 years, it has emerged that, while surgical revascularisation of extensive ischaemic heart disease may have prognostic advantages, the main issues considered regarding individual management are usually those of symptomatic improvement only. The major impetus towards invasive intervention is therefore failure of prophylactic anti-anginal therapy. On the other hand, many patients, especially the elderly, now present the clinical problem of ongoing angina without residual invasive options. There is an ongoing need for more effective anti-anginal therapies. Of the currently available major classes of prophylactic anti-anginal agents, neither nitrates, β-blockers nor calcium antagonists generally produce marked improvements in exercise duration. Three areas of new therapeutic development in anti-anginal therapy are worthy of note. These involve the sinus node inhibitor ivabradine, high dose allopurinol (xanthine oxidase inhibitor) and a new class of “metabolic modulators” represented by perhexiline, trimetazidine and probably ranolazine. The current review addresses the therapeutic potential of these agents. Notably, all of these “new” drugs are potentially suitable for management of angina in the setting of impaired left ventricular systolic function, and they may also be utilized in patients with angina independent of the presence of coronary disease (for example in hypertrophic cardiomyopathy). The current evidence for efficacy and potential future development in this area are reviewed.
文摘Oral dissolving gelatin beads (GBs) containing allopurinol (AP) were prepared by the seamless capsule method and their rheological properties were examined. The release profiles of both gelatin and AP from GBs were also investigated in limited dissolution medium. GBs containing AP provided an easy-to-handle dosage form, but the physical strength of the beads immediately decreased upon contact with physiological saline at 37℃. Gelatin was released from the outer layer of GBs in physiological saline, with almost all the gelatin dissolved after 5 min, together with approximately 30% of the AP contained in the inner layer of the GB. The oral administration of GBs likely results in immediate softening of the GB upon contact with saliva. The released AP acts directly at inflammation sites, in a manner similar following oral rinsing with an AP suspension. Therefore, GBs are a useful dosage form for preventing or treating localized problems in the oral cavity, such as mucositis.
文摘Introduction: The Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) syndrome is a very rare iatrogenic accident that is characterized by its difficult diagnosis due to its clinical latency and heterogeneous clinic. The form induced by allopurinol remains exceptional and often ignored by clinicians, although potentially fatal. We are reporting an original observation of allopurinol-induced DRESS syndrome in elderly. Case report: A 64-year-old woman who had been treated with allopurinol for gout for three weeks, was hospitalized for a diffuse, erythematous and maculopapular cutaneous rash, associated with fever at 39℃ , dyspnea, generalized lymphadenopathy, and a hyperkeratotic and desquamative plantar eruption. The biology showed eosinophilia at 860/mm3 and cytolitic hepatitis without cholestasis or hepatocellular insufficiency with ASAT at 230 IU/l and alanine aminotransferase ( ALAT) at 280 IU/l. The infectious, immunological investigation, as well as the search for underlying malignant neoplasia or hematological malignancy were negative. The skin biopsy was inconclusive. The diagnosis of a DRESS syndrome induced by allopurinol was retained. The evolution was rapidly favorable after stopping allopurinol and treatment with systemic glucocorticoids. Conclusion: The incidence of cutaneous reactions to allopurinol is estimated at 1.5/100,000 H/year. The DRESS syndrome, the most serious form of these reactions, remains exceptional. This particular form of toxicity deserves to be known by clinicians, especially since allopurinol is widely prescribed in the elderly.
基金The National Institute of Diabetes, Digestive and Kidney Diseases (NIDDK), DK069939 the Technology Transfer Grant (TTG) by UC Davis Medical Center to Wu J
文摘AIM: To determine the effects of allopurinol, an inhibitor of xanthine oxidase, and apocynin, an inhibitor of NADPH oxidase, on oxidant stress and liver injury caused by hepatic ischemia/reperfusion (I/R) procedure in mice. METHODS: Mice were pretreated with a xanthine oxidase inhibitor, allopurinol, or NADPH oxidase (NOX) inhibitor, apocynin before the hepatic I/R procedure. Then treated or untreated mice underwent the hepatic I/R procedure. The effects on hepatic injury and superoxide anions were determined after starting reperfusion. RESULTS: A standard warm hepatic I/R procedure led to a marked increase in superoxide anion production as indicated by a superoxide anion tracer, MCLA. At the same time, the procedure caused profound acute liver injury, as indicated by elevated serum alanine aminotransferase and tumor necrosis factor-α levels, reduced liver glutathione levels and elevated malondialdehyde contents, as well as a high apoptotic cell count. All these changes were reversed by the use of apocynin or allopurinol prior to the hepatic I/R procedure. CONCLUSION: Allopurinol and apocynin exerted protective effects on hepatic ischemia/reperfusion injury. The protection is associated with blocking the generationof superoxide anions during the hepatic I/R procedure by inhibiting xanthine oxidase and NADPH oxidase activity.
基金Qinhuangdao Science and Technology Research and Development Plan:Clinical Study of Rhubarb and Peony Decoction in the Treatment of Chronic Kidney Disease Stage 1-3 Complicated with Hyperuricemia(202101A203)。
文摘OBJECTIVE:To evaluate the effect of Dahuang Mudan Tang(大黄牡丹汤,DHMD)and allopurinol on the treatment of chronic kidney disease staged G1-G3b patients with hyperuricemia and to provide novel insights into the clinical management of chronic kidney disease complications.METHODS:A total of 80 chronic kidney patients staged G1-G3b with hyperuricemia were randomly grouped to receive single allopurinol treatment(control)and combined treatment with DHMD(treated)for 8 weeks.The kidney function and proteinuria indicators of patients were compared between pre-and post-treatment.The oxidative stress and inflammation responses were evaluated by corresponding indicators and cytokines.The clinical efficiency rate and adverse reaction events were also summarized to assess the therapeutic efficiency and safety.RESULTS:The kidney function and proteinuria of enrolled patients were alleviated after their therapies,behaved as the increasing estimated glomerular filtration rate and decreasing serum creatinine,serum uric acid,urea nitrogen,24 h urine protein levels.On the other hand,the malondialdehyde level and pro-inflammation cytokines were suppressed by the therapies,and the superoxide dismutase was found to be significantly enhanced.Patients in the treated groups showed a better recovery in kidney function,proteinuria,oxidative stress,and inflammation response.Moreover,patients in the treated group showed a higher efficiency rate(95%)and fewer adverse reaction events(5%).CONCLUSIONS:The combination of allopurinol with DHMD significantly promoted the recovery of chronic kidney disease stage G1-G3b patients with hyperuricemia,which can be considered a novel clinical therapeutic strategy.
