Safety and tolerability of available drugs for hyperuricemia: a critical review and an update on recent developments

doi:10.5246/jcps.2022.06.035

Abstract

Abstract:

Hyperuricemia (HUA) is a metabolic disease caused by excessive production of serum uric acid (sUA) or decreased excretion of sUA in the body. HUA is an independent risk factor for chronic kidney disease, hypertension, cardiovascular and cerebrovascular diseases, and diabetes mellitus. Timely and effective treatment for reducing sUA plays a key role in reducing urate deposition, preventing gout attacks, and reducing kidney damage and the occurrence of other accompanying diseases. Four pharmacological methods can be used to treat HUA: decrease urate production, increase urate excretion, prevent urate formation, and catabolize urate. To provide a reference for clinical treatment and new medical research for HUA, the drugs and potential drugs for HUA were reviewed in the present work.

Key words: Hyperuricemia, Serum uric acid, Drugs

Supporting:

Gong Fang, Wenxi Li, Jie Zhang, Qinghua Ke, Xinggui Zhu, Lihua Long, Changhai Li. Safety and tolerability of available drugs for hyperuricemia: a critical review and an update on recent developments[J]. Journal of Chinese Pharmaceutical Sciences, 2022, 31(6): 397-411.

References 86

[1]	Chinese Medical Association Endocrinology Branch. Guidelines for the diagnosis and treatment of hyperuricemia and gout in China. Chin. J. Endocrinol. Metab. 2020, 36, 1–13.
[2]	Major, T.J.; Dalbeth, N.; Stahl, E.A.; Merriman, T.R. An update on the genetics of hyperuricaemia and gout. Nat. Rev. Rheumatol. 2018, 14, 341–353.
[3]	Sun, L.; Wang, G.X.; Guo, W.Y. Research progress of hyperuricemia. Chin. J. Gerontol. 2017, 37, 1034–1038.
[4]	Pei, F.; Pei, H.; Xia, Z.H.; Xie, F.S.; Su, C.H. Advances in epigenetics of hyperuri-cemia and gout. Adv. Physiol. Sci. 2019, 50, 175–180.
[5]	Grayson, P.C.; Kim, S.Y.; LaValley, M.; Choi, H.K. Hyperuricemia and incident hypertension: a systematic review and meta-analysis. Arthritis Care Res. 2011, 63, 102–110.
[6]	Kuwabara, M.; Niwa, K.; Hisatome, I.; Nakagawa, T.; Roncal-Jimenez, C.A.; Andres-Hernando, A.; Bjornstad, P.; Jensen, T.; Sato, Y.; Milagres, T.; Garcia, G.; Ohno, M.; Lanaspa, M.A.; Johnson, R.J. Asymptomatic hyperuricemia without comorbidities predicts cardiometabolic diseases: five-year Japanese cohort study. Hypertens. Dallas Tex. 2017, 69, 1036–1044.
[7]	Wan, X.Y.; Zhang, F. Research progress in the application of traditional Chine-se medicine in the treatment of hyperuricemia. Diabetes World. 2020, 17, 264.
[8]	Lv, X.X.; Hu, J.D. Survey on the prevalence of hyperuricemia and analysis of i-ts clinical impact. J. Clin. Lab. Med. (Electronic Edition). 2020, 9, 34–35.
[9]	Sun, S.S.; Qu, L.Y.; Du, R.R.; Lin, J.Y. Research progress in drug treatment of hyperuricemia. Chin. J. Clin. Pharm. Ther. 2019, 24, 589–594.
[10]	Cicero, A.F.G.; Pirro, M.; Watts, G.F.; Mikhailidis, D.P.; Banach, M.; Sahebkar, A. Effects of allopurinol on endothelial function: a systematic review and meta-analysis of randomized placebo-controlled trials. Drugs. 2018, 78, 99–109.
[11]	Dubreuil, M.; Zhu, Y.; Zhang, Y.; Seeger, J.D.; Lu, N.; Rho, Y.H.; Choi, H.K. Allopurinol initiation and all-cause mortality in the general population. Ann. Rheum. Dis. 2015, 74, 1368–1372.
[12]	Grimaldi-Bensouda, L.; Alpérovitch, A.; Aubrun, E.; Danchin, N.; Rossignol, M.; Abenhaim, L.; Richette, P.; PGRx MI Group. Impact of allopurinol on risk of myocardial infarction. Ann. Rheum. Dis. 2015, 74, 836–842.
[13]	Kao, M.P.; Ang, D.S.; Gandy, S.J.; Nadir, M.A.; Houston, J.G.; Lang, C.C.; Struthers, A.D. Allopurinol benefits left ventricular mass and endothelial dysfunction in chronic kidney disease. J. Am. Soc. Nephrol. 2011, 22, 1382–1389.
[14]	Day, R.O.; Graham, G.G.; Hicks, M.; McLachlan, A.J.; Stocker, S.L.; Williams, K.M. Clinical pharmacokinetics and pharmacodynamics of allopurinol and oxypurinol. Clin. Pharmacokinet. 2007, 46, 623–644.
[15]	Khanna, D.; Fitzgerald, J.D.; Khanna, P.P.; Bae, S.; Singh, M.K.; Neogi, T.; Pillinger, M.H.; Merill, J.; Lee, S.; Prakash, S.; Kaldas, M.; Gogia, M.; Perez-Ruiz, F.; Taylor, W.; Lioté, F.; Choi, H.; Singh, J.A.; Dalbeth, N.; Kaplan, S.; Niyyar, V.; Jones, D.; Yarows, S.A.; Roessler, B.; Kerr, G.; King, C.; Levy, G.; Furst, D.E.; Edwards, N.L.; Mandell, B.; Schumacher, H.R.; Robbins, M.; Wenger, N.; Terkeltaub, R.; American College of Rheumatology. 2012 American College of Rheumatology guidelines for management of gout. Part 1: systematic nonpharmacologic and pharmacologic therapeutic approaches to hyperuricemia. Pharmacogenetics Genom. 2012, 64, 1431–1446.
[16]	Zhu, X.F.; Zou, H.J.; Fang, Y.; Wu, Y.B.; Yang, L.H.; Xia, R. Study of correlation between allopurinol-induced cutaneous adverse reactions and HLA-B^* 5801 gene. Chin. J. Blood Transfus. 2015, 28, 1023–1025.
[17]	Ye, P.; Yang, S.M.; Zhang, W.L.; Lv, Q.; Cheng, Q.F.; Mei, M.; Luo, T.; Liu, L.L.; Chen, S.M.; Li, Q.F. Efficacy and tolerability of febuxostat in hyperuricemic patients with or without gout: a systematic review and meta-analysis. Clin. Ther. 2013, 35, 180–189.
[18]	Ma, J.K.; Zhang, H.B. The research progress of hyperuricemia and its therapeutic drugs. Guangdong Med. J. 2018, 39, 262–267.
[19]	Schumacher, H.R. Jr, Becker, M.A.; Wortmann, R.L.; MacDonald, P.A.; Hunt, B.; Streit, J.; Lademacher, C.; Joseph-Ridge, N. Effects of febuxostat versus allopurinol and placebo in reducing serum urate in subjects with hyperuricemia and gout: a 28-week, phase III, randomized, double-blind, parallel-group trial. Arthritis Rheum. 2008, 59, 1540–1548.
[20]	Borghi, C.; Perez-Ruiz, F. Urate lowering therapies in the treatment of gout: a systematic review and meta-analysis. Eur. Rev. Med. Pharmacol. Sci. 2016, 20, 983–992.
[21]	Becker, M.A.; Schumacher, H.R. Jr, Wortmann, R.L.; MacDonald, P.A.; Eustace, D.; Palo, W.A.; Streit, J.; Joseph-Ridge, N. Febuxostat compared with allopurinol in patients with hyperuricemia and gout. N. Engl. J. Med. 2005, 353, 2450–2461.
[22]	van Echteld, I.A.; van Durme, C.; Falzon, L.; Landewé, R.B.; van der Heijde, D.M.; Aletaha, D. Treatment of gout patients with impairment of renal function: a systematic literature review. J. Rheumatol. Suppl. 2014, 92, 48–54.
[23]	Tang, Z.Y.; Qing, Y.F. The current status and research progress of serum uric acid-lowering drugs in the treatment of hyperuricemia and gout. Chin. J. Rheumatol. 2019, 03, 199–204.
[24]	White, W.B.; Saag, K.G.; Becker, M.A.; Borer, J.S.; Gorelick, P.B.; Whelton, A.; Hunt, B.; Castillo, M.; Gunawardhana, L.; CARES Investigators. Cardiovascular safety of febuxostat or allopurinol in patients with gout. N. Engl. J. Med. 2018, 378, 1200–1210.
[25]	Ohata, K.; Kamijo-Ikemori, A.; Sugaya, T.; Hibi, C.; Nakamura, T.; Murase, T.; Oikawa, T.; Hoshino, S.; Katayama, K.; Asano, J.; Kimura, K.; Shibagaki, Y. Renoprotective effect of the xanthine oxidoreductase inhibitor Topiroxostat under decreased angiotensin II type 1a receptor expression. Eur. J. Pharmacol. 2017, 815, 88–97.
[26]	Hosoya, T.; Ohno, I.; Nomura, S.; Hisatome, I.; Uchida, S.; Fujimori, S.; Yamamoto, T.; Hara, S. Effects of topiroxostat on the serum urate levels and urinary albumin excretion in hyperuricemic stage 3 chronic kidney disease patients with or without gout. Clin. Exp. Nephrol. 2014, 18, 876–884.
[27]	Hosoya, T.; Ogawa, Y.; Hashimoto, H.; Ohashi, T.; Sakamoto, R. Comparison of topiroxostat and allopurinol in Japanese hyperuricemic patients with or without gout: a phase 3, multicentre, randomized, double-blind, double-dummy, active-controlled, parallel-group study. J. Clin. Pharm. Ther. 2016, 41, 290–297.
[28]	Hosoya, T.; Ishikawa, T.; Ogawa, Y.; Sakamoto, R.; Ohashi, T. Multicenter, open-label study of long-term topiroxostat (FYX-051) administration in Japanese hyperuricemic patients with or without gout. Clin. Drug Investig. 2018, 38, 1135–1143.
[29]	Wada, T.; Hosoya, T.; Honda, D.; Sakamoto, R.; Narita, K.; Sasaki, T.; Okui, D.; Kimura, K. Uric acid-lowering and renoprotective effects of topiroxostat, a selective xanthine oxidoreductase inhibitor, in patients with diabetic nephropathy and hyperuricemia: a randomized, double-blind, placebo-controlled, parallel-group study (UPWARD study). Clin. Exp. Nephrol. 2018, 22, 860–870.
[30]	Nyberg, M.; Piil, P.; Kiehn, O.T.; Maagaard, C.; Jørgensen, T.S.; Egelund, J.; Isakson, B.E.; Nielsen, M.S.; Gliemann, L.; Hellsten, Y. Probenecid inhibits α-adrenergic receptor–mediated vasoconstriction in the human leg vasculature. Hypertension. 2018, 71, 151–159.
[31]	Barone, S.; Xu, J.; Zahedi, K.; Brooks, M.; Soleimani, M. Probenecid pre-treatment downregulates the kidney Cl^–/HCO₃^– exchanger (pendrin) and potentiates hydrochlorothiazide-induced diuresis. Front. Physiol. 2018, 9, 849.
[32]	Li, S.; Yang, H.X.; Guo, Y.N.; Wei, F.J.; Yang, X.L.; Li, D.Q.; Li, M.Z.; Xu, W.L.; Li, W.D.; Sun, L.; Gao, Y.; Wang, Y.G. Comparative efficacy and safety of urate-lowering therapy for the treatment of hyperuricemia: a systematic review and network meta-analysis. Sci. Rep. 2016, 6, 33082.
[33]	Finch, A.; Kubler, P. The management of gout. Aust. Prescr. 2016, 39, 119–122.
[34]	Strilchuk, L.; Fogacci, F.; Cicero, A.F. Safety and tolerability of available urate-lowering drugs: a critical review. Expert Opin. Drug Saf. 2019, 18, 261–271.
[35]	Zhou, Q.; Su, J.; Zhou, T.; Tian, J.; Chen, X.; Zhu, J. A study comparing the safety and efficacy of febuxostat, allopurinol, and benzbromarone in Chinese gout patients: a retrospective cohort study. Int. J. Clin. Pharmacol. Ther. 2017, 55, 163–168.
[36]	Chou, H.W.; Chiu, H.T.; Tsai, C.W.; Ting, I.W.; Yeh, H.C.; Huang, H.C.; Kuo, C.C.; Group, C.K.R. Comparative effectiveness of allopurinol, febuxostat and benzbromarone on renal function in chronic kidney disease patients with hyperuricemia: a 13-year inception cohort study. Nephrol. Dial. Transplant. 2017, 33, 1620–1627.
[37]	Endocrinology Branch of Chinese Medical Association. Guidelines for the diagnosis and treatment of hyperuricemia and gout in China (2019). Chin. J. Endocrinol. Metab. 2020, 01, 1–13.
[38]	Walls, M.; Goral, S.; Stone, W. Acute renal failure due to sulfinpyrazone. Am. J. Med. Sci. 1998, 315, 319–321.
[39]	Prior, C.; Kirchmair, H. Acute interstitial nephritis and kidney failure requiring dialysis after sulfinpyrazone therapy. Acta Medica Austriaca. 1984, 11, 55–59.
[40]	Lu, H.B.; Lu, C.H. Research progress of xanthine oxidase inhibitors for the treatment of hyperuricemia. Anhui Med. 2016, 20, 626–630.
[41]	Pascart, T.; Richette, P. Investigational drugs for hyperuricemia, an update on recent developments. Expert Opin. Investig. Drugs. 2018, 27, 437–444.
[42]	Bantia, S.; Harman, L.; Hollister, A.; Pearson, P. FRI0401 BCX4208, a novel enzyme inhibitor for chronic management of GOUT, shows a low risk of potential drug-drug interactions. Ann. Rheum. Dis. 2013, 71, 450.
[43]	Shahid, H.; Singh, J.A. Investigational drugs for hyperuricemia. Expert Opin. Investig. Drugs. 2015, 24, 1013–1030.
[44]	Hollister, A.S.; Dobo, S.; Maetzel, A.; Becker, M.A.; Terkeltaub, R.; Fitz-Patrick, D.; Smith, V.; Sheridan, W. FRI0380 Long-term safety of BCX4208 added to allopurinol in the chronic management of GOUT: results of a phase 2 24-week blinded safety extension and vaccine challenge study. Ann. Rheum. Dis. 2013, 71, 442.3–443.
[45]	Miner, J.N.; Tan, P.K.; Hyndman, D.; Liu, S.; Iverson, C.; Nanavati, P.; Hagerty, D.T.; Manhard, K.; Shen, Z.; Girardet, J.L.; Yeh, L.T.; Terkeltaub, R.; Quart, B. Lesinurad, a novel, oral compound for gout, acts to decrease serum uric acid through inhibition of urate transporters in the kidney. Arthritis Res. Ther. 2016, 18, 214.
[46]	Gillen, M.; Valdez, S.; Zhou, D.; Kerr, B.; Lee, C.A.; Shen, Z. Effects of renal function on pharmacokinetics and pharmacodynamics of lesinurad in adult volunteers. Drug Des. Dev. Ther. 2016, 10, 3555–3562.
[47]	Tausche, A.K.; Alten, R.; Dalbeth, N.; Kopicko, J.; Fung, M.; Adler, S.; Bhakta, N.; Storgard, C.; Baumgartner, S.; Saag, K. Lesinurad monotherapy in gout patients intolerant to a xanthine oxidase inhibitor: a 6 month phase 3 clinical trial and extension study. Rheumatology. 2017, 56, 2170–2178.
[48]	Chen, G.L.; Zhou, Y.F.; Zhang, Y. Research progress of drugs for the treatment of gout and hyperuricemia. Chin. J. Clin. Pharm. Ther. 2017, 22, 104.
[49]	Fitz-Patrick, D.; Roberson, K.; Niwa, K.; Fujimura, T.; Mori, K.; Hall, J.; Yan, X.H.; Shen, Z.C.; Liu, S.; Ito, Y.; Baumgartner, S. Safety and efficacy of verinurad, a selective URAT1 inhibitor, for the treatment of patients with gout and/or asymptomatic hyperuricemia in the United States and Japan: findings from two phase II trials. Mod. Rheumatol. 2019, 29, 1042–1052.
[50]	Wang, G.; Zuo, T.; Li, R. The mechanism of Arhalofenate in alleviating hyperuricemia-Activating PPARγ thereby reducing caspase-1 activity. Drug Dev. Res. 2020, 81, 859–866.
[51]	Karpf, G.; Choi, D.; Roberts, Y.J. Arhalofenate, a Potential Novel Treatment for Hyperuricemia, with or without Metabolic Co-Morbidities, in Patients with Gout: Meta-Analysis of Urate Lowering in Four Phase 2 Studies in Type 2 Diabetes. Arthritis Rheum. 2011, 63.
[52]	Steinberg, A.S.; Vince, B.D.; Choi, Y.J.; Martin, R.L.; McWherter, C.A.; Boudes, P.F. The pharmacodynamics, pharmacokinetics, and safety of arhalofenate in combination with febuxostat when treating hyperuricemia associated with gout. J. Rheumatol. 2017, 44, 374–379.
[53]	Immune molecular and inflammatory cytokines dysfunction analysis in gout patients with different urate levels. Available from https://clinicaltrials.gov/ct2/show/NCT02060552.
[54]	Yu, Y.K.; Yu, F.; Ye, C.; Shen, G.F.; Lei, X.M.; Zhang, S.T.; Hu, S.X. Combination therapies of diacerein and febuxostat inhibit IL-1β responses and improve clinical symptoms in patients with refractory gout. Am. J. Ther. 2017, 24, e290–e297.
[55]	Sands, E.; Kivitz, A.J.; DeHaan, W.; Johnston, L.; Kishimoto, T.K. Initial phase 2 clinical data of SEL-212 in symptomatic gout patients: monthly dosing of a pegylated uricase (pegsiticase) with SVP-rapamycin enables sustained reduction of serum uric acid levels by mitigating formation of anti-drug antibodies. In Arthritis & rheumatology. 2017, 111 RIVER ST, HOBOKEN 07030–5774.
[56]	Noveck, R.; Wang, Z.; Forsthoefel, A.; Sigmon, K.; Hall, P.; Keogh, J.; Sundy, J. Levotofisopam Has Uricosuric Activity and Reduces Serum Urate Levels in Patients with Gout. Arthritis Rheum. 2012, 818, 64.
[57]	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, 160–164.
[58]	Warrell, R.; Klukovits, A.; Barnes, K.; Satyanarayana, C.; Cheeseman, C.; Piwinski, J. Profound Hypouricemia Induced in Human Subjects By Novel Bifunctional Inhibitors of Xanthine Oxidase and URAT1. Arthritis Rheum. 2014, 66, 830.
[59]	Warrell, R.P. Jr, Muindi, J.; Stevens, Y.W.; Isaacs, M.; Young, C.W. Induction of profound hypouricemia by a non-sedating thiobarbiturate. Metabolism. 1989, 38, 550–554.
[60]	Warrell, R.P.; Jr. Methods for reducing uric acid levels using barbiturate derivatives. US Patent 9428466 [P]. 2016-08-30.
[61]	Dua, P.; Gurrell, R.; Kirby, S.; Sudworth, M.; Loudon, P.T. Acute kidney injury observed during phase 1 clinical trials of a novel xanthine oxidase/URAT1 dual inhibitor PF-06743649. Clin. Rheumatol. 2016, 35, 2045–2051.
[62]	Ahn, S.O.; Ohtomo, S.; Kiyokawa, J.; Nakagawa, T.; Yamane, M.; Lee, K.J.; Kim, K.H.; Kim, B.H.; Tanaka, J.; Kawabe, Y.; Horiba, N. Stronger uricosuric effects of the novel selective URAT1 inhibitor UR-1102 lowered plasma urate in tufted capuchin monkeys to a greater extent than benzbromarone. J. Pharmacol. Exp. Ther. 2016, 357, 157–166.
[63]	Taniguchi, T.; Ashizawa, N.; Matsumoto, K.; Iwanaga, T. Enhancement of pharmacological effects of uricosuric agents by concomitant treatment with pyrazinamide in rats. Naunyn Schmiedeberg’s Arch. Pharmacol. 2017, 390, 253–260.
[64]	Taniguchi, T.; Ashizawa, N.; Matsumoto, K.; Iwanaga, T.; Saitoh, K. Uricosuric agents decrease the plasma urate level in rats by concomitant treatment with topiroxostat, a novel xanthine oxidoreductase inhibitor. J. Pharm. Pharmacol. 2015, 68, 76–83.
[65]	Mandal, A.K.; Mercado, A.; Foster, A.; Zandi-Nejad, K.; Mount, D.B. Uricosuric targets of tranilast. Pharmacol. Res. Perspect. 2017, 5, e00291.
[66]	Jimbo, R.; Yoshioka, A.; Takahashi, Y.; Ono, K.; Adachi, Y.; Kojima, S.; Takeda, Y.; Nouch, T.; Shimizu, S. Five cases of drug-induced liver injury by tranilast. Nihon Shokakibyo Gakkai Zasshi. 2005, 102, 1051–1054.
[67]	Nagae, S.; Hori, Y. Immune thrombocytopenia due to Tranilast (Rizaben): detection of drug-dependent platelet-associated IgG. J. Dermatol. 1998, 25, 706–709.
[68]	Sakai, N.; Yamada, T.; Murayama, T. Eosinophilic cystitis induced by tranilast: a case report. Acta urologica Japonica. 1998, 44, 45–47.
[69]	Arase, S.; Kato, S.; Nakanishi, H.; Sadamoto, Y.; Urano, Y.; Kawai, H.; Takeda, K. Eosinophilic polymyositis induced by tranilast. J. Dermatol. 1990, 17, 182–186.
[70]	Du, G.; Jiang, Y.T.; Gu, J.R. Research progress of serum uric acid-lowering drugs. New Med. 2017, 48, 369–374.
[71]	Huang, L.H.; Jiang, Y.; Lou, J.R. Evaluation of clinical efficacy and safety of urate oxidase. Int. J. Biol. 2016, 39, 92–96.
[72]	Jayabose, S.; Kumar, V.; Dhanabalan, R.; Rajan, P.; Rathnam, K.; Viswanathan, T.K. Low-dose rasburicase in hematologic malignancies. Indian J. Pediatr. 2015, 82, 458–461.
[73]	Sestigiani, E.; Mandreoli, M.; Guardigli, M.; Roda, A.; Ramazzotti, E.; Boni, P.; Santoro, A. Efficacy and (pharmaco)kinetics of one single dose of rasburicase in patients with chronic kidney disease. Nephron Clin. Pract. 2008, 108, c265–c271.
[74]	Boutin, A.; Blackman, A.; O'Sullivan, D.M.; Forcello, N. The value of fixed rasburicase dosing versus weight-based dosing in the treatment and prevention of tumor lysis syndrome. J. Oncol. Pharm. Pract. 2019, 25, 577–583.
[75]	Philips, A.; Radhakrishnan, V.; Ganesan, P.; Ganesan, T.S.; Ramamurthy, J.; Dhanushkodi, M.; Sagar, T.G. Efficacy of single dose rasburicase (1.5 mg) for prophylaxis and management of laboratory tumor lysis syndrome. Indian J. Hematol. Blood Transfus. 2018, 34, 618–622.
[76]	Hill, C.L.; Lu, T.Y.; Cervelli, M.; Mathew, T. Failure of rasburicase therapy in recurrent acute gout with tophi. Int. J. Rheum. Dis. 2008, 11, 315–317.
[77]	Shannon, J.A.; Cole, S.W. Pegloticase: a novel agent for treatment-refractory gout. Ann. Pharmacother. 2012, 46, 368–376.
[78]	Yood, R.A.; Ottery, F.D.; Irish, W.; Wolfson, M. Effect of pegloticase on renal function in patients with chronic kidney disease: a post hoc subgroup analysis of 2 randomized, placebo-controlled, phase 3 clinical trials. BMC Res. Notes. 2014, 7, 54.
[79]	Reinders, M.K.; Jansen, T.L. New advances in the treatment of gout: review of pegloticase. Ther. Clin. Risk Manag. 2010, 6, 543–550.
[80]	Strilchuk, L.; Fogacci, F.; Cicero, A.F. Safety and tolerability of available urate-lowering drugs: a critical review. Expert Opin. Drug Saf. 2019, 18, 261–271.
[81]	Ea, H.K.; Richette, P. Critical appraisal of the role of pegloticase in the management of gout. Open Access Rheumatol. 2012, 4, 63–70.
[82]	Stamp, L.K.; Merriman, T.R.; Singh, J.A. Expert opinion on emerging urate-lowering therapies. Expert Opin. Emerg. Drugs. 2018, 23, 201–209.
[83]	Safety and pharmacodynamics of SEL-037 (Pegsiticase) in subjects with elevated blood serum uric acid levels. Bethesda, MD: Clinicaltrials.gov; 2016. Available from https://clinicaltrials.gov/ct2/show/NCT02464605.
[84]	Xiong, X.H.; Zhang, X.Z. Research on Losartan Potassium in the Treatment of Essential Hypertension with Left Ventricular Hypertrophy and Hyperuricemia. Jiangxi Med. 2020, 55, 1655–1656.
[85]	You, Y.; Qi, G.Y.; Gao, H.Y.; Yang, Z.Y.; Li, L.; Zhao, H.L. Effects of pivastatin on serum uric acid, inflammatory factors and vascular endothelial function in hyperuricemia rats. Chin. J. Immunol. 2020, 36, 2361
[86]	Chen, C.X.; Li, R. Research progress on the effect of SGLT2 inhibitors on serum uric acid. Modern Clin. Med. 2021, 47, 147–149.