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The role of urate and xanthine oxidase in vascular oxidative stress: future directions.

Therapeutics and clinical risk management

George J, Struthers A.
PMID: 19851527
Ther Clin Risk Manag. 2009;5:799-803. doi: 10.2147/tcrm.s5701. Epub 2009 Oct 12.

Vascular oxidative stress has been shown to be a potent factor in the pathophysiology of endothelial dysfunction. Despite current optimal evidence-based therapy, mortality from various cardiovascular disorders remains high. The search for newer, novel ways of attenuating endothelial dysfunction...

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George J, Struthers A. The role of urate and xanthine oxidase in vascular oxidative stress: future directions. Ther Clin Risk Manag. 2009;5:799-803doi: 10.2147/tcrm.s5701.
George, J., & Struthers, A. (2009). The role of urate and xanthine oxidase in vascular oxidative stress: future directions. Therapeutics and clinical risk management, 5799-803. https://doi.org/10.2147/tcrm.s5701
George, Jacob, and Struthers, Allan. "The role of urate and xanthine oxidase in vascular oxidative stress: future directions." Therapeutics and clinical risk management vol. 5 (2009): 799-803. doi: https://doi.org/10.2147/tcrm.s5701
George J, Struthers A. The role of urate and xanthine oxidase in vascular oxidative stress: future directions. Ther Clin Risk Manag. 2009;5:799-803. doi: 10.2147/tcrm.s5701. Epub 2009 Oct 12. PMID: 19851527; PMCID: PMC2762438.
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Simultaneous analysis of allopurinol and oxypurinol using a validated liquid chromatography-tandem mass spectrometry method in human plasma.

Journal of pharmaceutical analysis

Rathod DM, Patel KR, Mistri HN, Jangid AG, Shrivastav PS, Sanyal M.
PMID: 29404018
J Pharm Anal. 2017 Feb;7(1):56-62. doi: 10.1016/j.jpha.2016.05.005. Epub 2016 May 26.

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) of 100...

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Rathod DM, Patel KR, Mistri HN, et al. Simultaneous analysis of allopurinol and oxypurinol using a validated liquid chromatography-tandem mass spectrometry method in human plasma. J Pharm Anal. 2016;7(1):56-62doi: 10.1016/j.jpha.2016.05.005.
Rathod, D. M., Patel, K. R., Mistri, H. N., Jangid, A. G., Shrivastav, P. S., & Sanyal, M. (2017). Simultaneous analysis of allopurinol and oxypurinol using a validated liquid chromatography-tandem mass spectrometry method in human plasma. Journal of pharmaceutical analysis, 7(1), 56-62. https://doi.org/10.1016/j.jpha.2016.05.005
Rathod, Dhiraj M, et al. "Simultaneous analysis of allopurinol and oxypurinol using a validated liquid chromatography-tandem mass spectrometry method in human plasma." Journal of pharmaceutical analysis vol. 7,1 (2017): 56-62. doi: https://doi.org/10.1016/j.jpha.2016.05.005
Rathod DM, Patel KR, Mistri HN, Jangid AG, Shrivastav PS, Sanyal M. Simultaneous analysis of allopurinol and oxypurinol using a validated liquid chromatography-tandem mass spectrometry method in human plasma. J Pharm Anal. 2017 Feb;7(1):56-62. doi: 10.1016/j.jpha.2016.05.005. Epub 2016 May 26. PMID: 29404018; PMCID: PMC5686867.
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Reduction of Leukocyte Microvascular Adherence and Preservation of Blood-Brain Barrier Function by Superoxide-Lowering Therapies in a Piglet Model of Neonatal Asphyxia.

Frontiers in neurology

Ruden JB, Quick KL, Gonzales ER, Shah AR, Park TS, Kennedy N, Dugan LL, Gidday JM.
PMID: 31118919
Front Neurol. 2019 May 01;10:447. doi: 10.3389/fneur.2019.00447. eCollection 2019.

No abstract available.

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Ruden JB, Quick KL, Gonzales ER, et al. Reduction of Leukocyte Microvascular Adherence and Preservation of Blood-Brain Barrier Function by Superoxide-Lowering Therapies in a Piglet Model of Neonatal Asphyxia. Front Neurol. 2019;10:447doi: 10.3389/fneur.2019.00447.
Ruden, J. B., Quick, K. L., Gonzales, E. R., Shah, A. R., Park, T. S., Kennedy, N., Dugan, L. L., & Gidday, J. M. (2019). Reduction of Leukocyte Microvascular Adherence and Preservation of Blood-Brain Barrier Function by Superoxide-Lowering Therapies in a Piglet Model of Neonatal Asphyxia. Frontiers in neurology, 10447. https://doi.org/10.3389/fneur.2019.00447
Ruden, Jacob B, et al. "Reduction of Leukocyte Microvascular Adherence and Preservation of Blood-Brain Barrier Function by Superoxide-Lowering Therapies in a Piglet Model of Neonatal Asphyxia." Frontiers in neurology vol. 10 (2019): 447. doi: https://doi.org/10.3389/fneur.2019.00447
Ruden JB, Quick KL, Gonzales ER, Shah AR, Park TS, Kennedy N, Dugan LL, Gidday JM. Reduction of Leukocyte Microvascular Adherence and Preservation of Blood-Brain Barrier Function by Superoxide-Lowering Therapies in a Piglet Model of Neonatal Asphyxia. Front Neurol. 2019 May 01;10:447. doi: 10.3389/fneur.2019.00447. eCollection 2019. PMID: 31118919; PMCID: PMC6504682.
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Oxypurinol pharmacokinetics and pharmacodynamics in healthy volunteers: Influence of BCRP Q141K polymorphism and patient characteristics.

Clinical and translational science

Vora B, Brackman DJ, Zou L, Garcia-Cremades M, Sirota M, Savic RM, Giacomini KM.
PMID: 33931953
Clin Transl Sci. 2021 Jul;14(4):1431-1443. doi: 10.1111/cts.12992. Epub 2021 May 01.

The missense variant, breast cancer resistance protein (BCRP) p.Q141K, which encodes a reduced function BCRP, has been linked to poor response to allopurinol. Using a multifaceted approach, we aimed to characterize the relationship(s) between BCRP p.Q141K, the pharmacokinetics (PK)...

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Vora B, Brackman DJ, Zou L, et al. Oxypurinol pharmacokinetics and pharmacodynamics in healthy volunteers: Influence of BCRP Q141K polymorphism and patient characteristics. Clin Transl Sci. 2021;14(4):1431-1443doi: 10.1111/cts.12992.
Vora, B., Brackman, D. J., Zou, L., Garcia-Cremades, M., Sirota, M., Savic, R. M., & Giacomini, K. M. (2021). Oxypurinol pharmacokinetics and pharmacodynamics in healthy volunteers: Influence of BCRP Q141K polymorphism and patient characteristics. Clinical and translational science, 14(4), 1431-1443. https://doi.org/10.1111/cts.12992
Vora, Bianca, et al. "Oxypurinol pharmacokinetics and pharmacodynamics in healthy volunteers: Influence of BCRP Q141K polymorphism and patient characteristics." Clinical and translational science vol. 14,4 (2021): 1431-1443. doi: https://doi.org/10.1111/cts.12992
Vora B, Brackman DJ, Zou L, Garcia-Cremades M, Sirota M, Savic RM, Giacomini KM. Oxypurinol pharmacokinetics and pharmacodynamics in healthy volunteers: Influence of BCRP Q141K polymorphism and patient characteristics. Clin Transl Sci. 2021 Jul;14(4):1431-1443. doi: 10.1111/cts.12992. Epub 2021 May 01. PMID: 33931953; PMCID: PMC8301548.
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Pharmacokinetic/Pharmacodynamic Modelling of Allopurinol, its Active Metabolite Oxypurinol, and Biomarkers Hypoxanthine, Xanthine and Uric Acid in Hypoxic-Ischemic Encephalopathy Neonates.

Clinical pharmacokinetics

Chu WY, Annink KV, Nijstad AL, Maiwald CA, Schroth M, Bakkali LE, van Bel F, Benders MJNL, van Weissenbruch MM, Hagen A, Franz AR, Dorlo TPC, Allegaert K, Huitema ADR.
PMID: 34617261
Clin Pharmacokinet. 2021 Oct 07; doi: 10.1007/s40262-021-01068-0. Epub 2021 Oct 07.

BACKGROUND: Allopurinol, an xanthine oxidase (XO) inhibitor, is a promising intervention that may provide neuroprotection for neonates with hypoxic-ischemic encephalopathy (HIE). Currently, a double-blind, placebo-controlled study (ALBINO, NCT03162653) is investigating the neuroprotective effect of allopurinol in HIE neonates.OBJECTIVE: The...

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Chu WY, Annink KV, Nijstad AL, et al. Pharmacokinetic/Pharmacodynamic Modelling of Allopurinol, its Active Metabolite Oxypurinol, and Biomarkers Hypoxanthine, Xanthine and Uric Acid in Hypoxic-Ischemic Encephalopathy Neonates. Clin Pharmacokinet. 2021;doi: 10.1007/s40262-021-01068-0.
Chu, W. Y., Annink, K. V., Nijstad, A. L., Maiwald, C. A., Schroth, M., Bakkali, L. E., van Bel, F., Benders, M. J. N. L., van Weissenbruch, M. M., Hagen, A., Franz, A. R., Dorlo, T. P. C., Allegaert, K., Huitema, A. D. R. (2021). Pharmacokinetic/Pharmacodynamic Modelling of Allopurinol, its Active Metabolite Oxypurinol, and Biomarkers Hypoxanthine, Xanthine and Uric Acid in Hypoxic-Ischemic Encephalopathy Neonates. Clinical pharmacokinetics, . https://doi.org/10.1007/s40262-021-01068-0
Chu, Wan-Yu, et al. "Pharmacokinetic/Pharmacodynamic Modelling of Allopurinol, its Active Metabolite Oxypurinol, and Biomarkers Hypoxanthine, Xanthine and Uric Acid in Hypoxic-Ischemic Encephalopathy Neonates." Clinical pharmacokinetics vol. (2021). doi: https://doi.org/10.1007/s40262-021-01068-0
Chu WY, Annink KV, Nijstad AL, Maiwald CA, Schroth M, Bakkali LE, van Bel F, Benders MJNL, van Weissenbruch MM, Hagen A, Franz AR, Dorlo TPC, Allegaert K, Huitema ADR. Pharmacokinetic/Pharmacodynamic Modelling of Allopurinol, its Active Metabolite Oxypurinol, and Biomarkers Hypoxanthine, Xanthine and Uric Acid in Hypoxic-Ischemic Encephalopathy Neonates. Clin Pharmacokinet. 2021 Oct 07; doi: 10.1007/s40262-021-01068-0. Epub 2021 Oct 07. PMID: 34617261.
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Nuclear Magnetic Resonance Metabolomics Biomarkers for Identifying High Risk Patients with Extranodal Extension in Oral Squamous Cell Carcinoma.

Journal of clinical medicine

Tsai CK, Lin CY, Kang CJ, Liao CT, Wang WL, Chiang MH, Yen TC, Lin G.
PMID: 32235493
J Clin Med. 2020 Mar 30;9(4). doi: 10.3390/jcm9040951.

Extranodal extension (ENE) is an independent adverse prognostic factor in oral squamous cell carcinoma (OSCC), and is difficult to identify preoperatively. We aimed to discover biomarkers for high risk patients with ENE. Tandem tissue, plasma, and urine samples of...

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Tsai CK, Lin CY, Kang CJ, et al. Nuclear Magnetic Resonance Metabolomics Biomarkers for Identifying High Risk Patients with Extranodal Extension in Oral Squamous Cell Carcinoma. J Clin Med. 2020;9(4)doi: 10.3390/jcm9040951.
Tsai, C. K., Lin, C. Y., Kang, C. J., Liao, C. T., Wang, W. L., Chiang, M. H., Yen, T. C., & Lin, G. (2020). Nuclear Magnetic Resonance Metabolomics Biomarkers for Identifying High Risk Patients with Extranodal Extension in Oral Squamous Cell Carcinoma. Journal of clinical medicine, 9(4), . https://doi.org/10.3390/jcm9040951
Tsai, Cheng-Kun, et al. "Nuclear Magnetic Resonance Metabolomics Biomarkers for Identifying High Risk Patients with Extranodal Extension in Oral Squamous Cell Carcinoma." Journal of clinical medicine vol. 9,4 (2020). doi: https://doi.org/10.3390/jcm9040951
Tsai CK, Lin CY, Kang CJ, Liao CT, Wang WL, Chiang MH, Yen TC, Lin G. Nuclear Magnetic Resonance Metabolomics Biomarkers for Identifying High Risk Patients with Extranodal Extension in Oral Squamous Cell Carcinoma. J Clin Med. 2020 Mar 30;9(4). doi: 10.3390/jcm9040951. PMID: 32235493; PMCID: PMC7230778.
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Maternal-to-fetal allopurinol transfer and xanthine oxidase suppression in the late gestation pregnant rat.

Physiological reports

Kane AD, Camm EJ, Richter HG, Lusby C, Tijsseling D, Kaandorp JJ, Derks JB, Ozanne SE, Giussani DA.
PMID: 24400158
Physiol Rep. 2013 Nov;1(6):e00156. doi: 10.1002/phy2.156. Epub 2013 Nov 13.

Fetal brain hypoxic injury remains a concern in high-risk delivery. There is significant clinical interest in agents that may diminish neuronal damage during birth asphyxia, such as in allopurinol, an inhibitor of the prooxidant enzyme xanthine oxidase. Here, we...

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Kane AD, Camm EJ, Richter HG, et al. Maternal-to-fetal allopurinol transfer and xanthine oxidase suppression in the late gestation pregnant rat. Physiol Rep. 2013;1(6):e00156doi: 10.1002/phy2.156.
Kane, A. D., Camm, E. J., Richter, H. G., Lusby, C., Tijsseling, D., Kaandorp, J. J., Derks, J. B., Ozanne, S. E., & Giussani, D. A. (2013). Maternal-to-fetal allopurinol transfer and xanthine oxidase suppression in the late gestation pregnant rat. Physiological reports, 1(6), e00156. https://doi.org/10.1002/phy2.156
Kane, Andrew D, et al. "Maternal-to-fetal allopurinol transfer and xanthine oxidase suppression in the late gestation pregnant rat." Physiological reports vol. 1,6 (2013): e00156. doi: https://doi.org/10.1002/phy2.156
Kane AD, Camm EJ, Richter HG, Lusby C, Tijsseling D, Kaandorp JJ, Derks JB, Ozanne SE, Giussani DA. Maternal-to-fetal allopurinol transfer and xanthine oxidase suppression in the late gestation pregnant rat. Physiol Rep. 2013 Nov;1(6):e00156. doi: 10.1002/phy2.156. Epub 2013 Nov 13. PMID: 24400158; PMCID: PMC3871471.
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Pharmacodynamic and pharmacokinetic effects and safety of verinurad in combination with allopurinol in adults with gout: a phase IIa, open-label study.

RMD open

Fleischmann R, Winkle P, Miner JN, Yan X, Hicks L, Valdez S, Hall J, Liu S, Shen Z, Gillen M, Hernandez-Illas M.
PMID: 29531784
RMD Open. 2018 Feb 08;4(1):e000584. doi: 10.1136/rmdopen-2017-000584. eCollection 2018.

OBJECTIVES: Verinurad (RDEA3170) is a high affinity, selective uric acid transporter (URAT1) inhibitor indevelopment for treating gout and asymptomatic hyperuricaemia. This phase IIa study evaluated the pharmacodynamics, pharmacokinetics and safety of verinurad combined with allopurinol versus allopurinol alone in...

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Fleischmann R, Winkle P, Miner JN, et al. Pharmacodynamic and pharmacokinetic effects and safety of verinurad in combination with allopurinol in adults with gout: a phase IIa, open-label study. RMD Open. 2018;4(1):e000584doi: 10.1136/rmdopen-2017-000584.
Fleischmann, R., Winkle, P., Miner, J. N., Yan, X., Hicks, L., Valdez, S., Hall, J., Liu, S., Shen, Z., Gillen, M., & Hernandez-Illas, M. (2018). Pharmacodynamic and pharmacokinetic effects and safety of verinurad in combination with allopurinol in adults with gout: a phase IIa, open-label study. RMD open, 4(1), e000584. https://doi.org/10.1136/rmdopen-2017-000584
Fleischmann, Roy, et al. "Pharmacodynamic and pharmacokinetic effects and safety of verinurad in combination with allopurinol in adults with gout: a phase IIa, open-label study." RMD open vol. 4,1 (2018): e000584. doi: https://doi.org/10.1136/rmdopen-2017-000584
Fleischmann R, Winkle P, Miner JN, Yan X, Hicks L, Valdez S, Hall J, Liu S, Shen Z, Gillen M, Hernandez-Illas M. Pharmacodynamic and pharmacokinetic effects and safety of verinurad in combination with allopurinol in adults with gout: a phase IIa, open-label study. RMD Open. 2018 Feb 08;4(1):e000584. doi: 10.1136/rmdopen-2017-000584. eCollection 2018. PMID: 29531784; PMCID: PMC5845419.
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Febuxostat improves outcome in a rat model of cancer cachexia.

Journal of cachexia, sarcopenia and muscle

Konishi M, Pelgrim L, Tschirner A, Baumgarten A, von Haehling S, Palus S, Doehner W, Anker SD, Springer J.
PMID: 26136193
J Cachexia Sarcopenia Muscle. 2015 Jun;6(2):174-80. doi: 10.1002/jcsm.12017. Epub 2015 Apr 21.

BACKGROUND: Activity of xanthine oxidase is induced in cancer cachexia, and its inhibition by allopurinol or oxypurinol improves survival and reduces wasting in the Yoshida hepatoma cancer cachexia model. Here, we tested the effects of the second-generation xanthine oxidase...

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Konishi M, Pelgrim L, Tschirner A, et al. Febuxostat improves outcome in a rat model of cancer cachexia. J Cachexia Sarcopenia Muscle. 2015;6(2):174-80doi: 10.1002/jcsm.12017.
Konishi, M., Pelgrim, L., Tschirner, A., Baumgarten, A., von Haehling, S., Palus, S., Doehner, W., Anker, S. D., & Springer, J. (2015). Febuxostat improves outcome in a rat model of cancer cachexia. Journal of cachexia, sarcopenia and muscle, 6(2), 174-80. https://doi.org/10.1002/jcsm.12017
Konishi, Masaaki, et al. "Febuxostat improves outcome in a rat model of cancer cachexia." Journal of cachexia, sarcopenia and muscle vol. 6,2 (2015): 174-80. doi: https://doi.org/10.1002/jcsm.12017
Konishi M, Pelgrim L, Tschirner A, Baumgarten A, von Haehling S, Palus S, Doehner W, Anker SD, Springer J. Febuxostat improves outcome in a rat model of cancer cachexia. J Cachexia Sarcopenia Muscle. 2015 Jun;6(2):174-80. doi: 10.1002/jcsm.12017. Epub 2015 Apr 21. PMID: 26136193; PMCID: PMC4458083.
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Acute Effects of Oral Tofisopam on Plasma Concentration and Urinary Excretion of Uric Acid and Oxypurinol "Preliminary Communication".

Current clinical pharmacology

Hatayama M, Sumida C, Kurajoh M, Shiraishi J, Okazaki H, Shoji T, Koyama H, Tsutsumi Z, Moriwaki Y, Namba M, Yamamoto T.
PMID: 25619490
Curr Clin Pharmacol. 2015;10(2):160-164. doi: 10.2174/1574884710666150126143421.

The effects of tofisopam, a GABA-receptor agonist, following oral administration (300mg) with and without allopurinol pretreatment on the plasma concentration and renal transport of uric acid and oxypurinol were investigated in 5 healthy subjects. Fractional and urinary excretions of...

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Hatayama M, Sumida C, Kurajoh M, et al. Acute Effects of Oral Tofisopam on Plasma Concentration and Urinary Excretion of Uric Acid and Oxypurinol "Preliminary Communication". Curr Clin Pharmacol. 2015;10(2):160-164doi: 10.2174/1574884710666150126143421.
Hatayama, M., Sumida, C., Kurajoh, M., Shiraishi, J., Okazaki, H., Shoji, T., Koyama, H., Tsutsumi, Z., Moriwaki, Y., Namba, M., & Yamamoto, T. (2015). Acute Effects of Oral Tofisopam on Plasma Concentration and Urinary Excretion of Uric Acid and Oxypurinol "Preliminary Communication". Current clinical pharmacology, 10(2), 160-164. https://doi.org/10.2174/1574884710666150126143421
Hatayama, Miki, et al. "Acute Effects of Oral Tofisopam on Plasma Concentration and Urinary Excretion of Uric Acid and Oxypurinol "Preliminary Communication"." Current clinical pharmacology vol. 10,2 (2015): 160-164. doi: https://doi.org/10.2174/1574884710666150126143421
Hatayama M, Sumida C, Kurajoh M, Shiraishi J, Okazaki H, Shoji T, Koyama H, Tsutsumi Z, Moriwaki Y, Namba M, Yamamoto T. Acute Effects of Oral Tofisopam on Plasma Concentration and Urinary Excretion of Uric Acid and Oxypurinol "Preliminary Communication". Curr Clin Pharmacol. 2015;10(2):160-164. doi: 10.2174/1574884710666150126143421. PMID: 25619490.
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Mechanism for the increased permeability in endothelial monolayers induced by elastase.

Mediators of inflammation

Suzuki N, Ishii Y, Kitamura S.
PMID: 18472917
Mediators Inflamm. 1994;3(1):11-6. doi: 10.1155/S0962935194000025.

The aim of this study was to investigate the mechanism for the increase in endothelial permeability induced by human neutrophil elastase (HNE). Pretreatment of bovine pulmonary artery endothelial cells (BPAEC) with HNE(0-30 mug/ml) for 1 h produced a concentration...

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Suzuki N, Ishii Y, Kitamura S. Mechanism for the increased permeability in endothelial monolayers induced by elastase. Mediators Inflamm. 1994;3(1):11-6doi: 10.1155/S0962935194000025.
Suzuki, N., Ishii, Y., & Kitamura, S. (1994). Mechanism for the increased permeability in endothelial monolayers induced by elastase. Mediators of inflammation, 3(1), 11-6. https://doi.org/10.1155/S0962935194000025
Suzuki, N, et al. "Mechanism for the increased permeability in endothelial monolayers induced by elastase." Mediators of inflammation vol. 3,1 (1994): 11-6. doi: https://doi.org/10.1155/S0962935194000025
Suzuki N, Ishii Y, Kitamura S. Mechanism for the increased permeability in endothelial monolayers induced by elastase. Mediators Inflamm. 1994;3(1):11-6. doi: 10.1155/S0962935194000025. PMID: 18472917; PMCID: PMC2367014.
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The effects of the xanthine oxidase inhibitors, allopurinol and oxypurinol on the pattern of purine release from hypoxic rat cerebral cortex.

Neurochemistry international

O'Regan MH, Phillis JW, Walter GA.
PMID: 20504405
Neurochem Int. 1989;14(1):91-9. doi: 10.1016/0197-0186(89)90015-6.

Release of purines from the normoxic and hypoxic/ischemic rat cerebral cortex was studied with the cortical cup technique. Both allopurinol (100 mg/kg, i.v.) and its active metabolite oxypurinol (20 mg/kg, i.v.) reduced the release of uric acid to 10%...

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O'Regan MH, Phillis JW, Walter GA. The effects of the xanthine oxidase inhibitors, allopurinol and oxypurinol on the pattern of purine release from hypoxic rat cerebral cortex. Neurochem Int. 1989;14(1):91-9doi: 10.1016/0197-0186(89)90015-6.
O'Regan, M. H., Phillis, J. W., & Walter, G. A. (1989). The effects of the xanthine oxidase inhibitors, allopurinol and oxypurinol on the pattern of purine release from hypoxic rat cerebral cortex. Neurochemistry international, 14(1), 91-9. https://doi.org/10.1016/0197-0186(89)90015-6
O'Regan, M H, et al. "The effects of the xanthine oxidase inhibitors, allopurinol and oxypurinol on the pattern of purine release from hypoxic rat cerebral cortex." Neurochemistry international vol. 14,1 (1989): 91-9. doi: https://doi.org/10.1016/0197-0186(89)90015-6
O'Regan MH, Phillis JW, Walter GA. The effects of the xanthine oxidase inhibitors, allopurinol and oxypurinol on the pattern of purine release from hypoxic rat cerebral cortex. Neurochem Int. 1989;14(1):91-9. doi: 10.1016/0197-0186(89)90015-6. PMID: 20504405.
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