{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,27]],"date-time":"2026-06-27T09:31:04Z","timestamp":1782552664780,"version":"3.54.5"},"reference-count":76,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2023,8,21]],"date-time":"2023-08-21T00:00:00Z","timestamp":1692576000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea (NRF)","doi-asserted-by":"publisher","award":["NRF-2018R1A5A2023127"],"award-info":[{"award-number":["NRF-2018R1A5A2023127"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea (NRF)","doi-asserted-by":"publisher","award":["NRF-2021R1A2C1094462"],"award-info":[{"award-number":["NRF-2021R1A2C1094462"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Febuxostat (FBX), a selective xanthine oxidase inhibitor, belongs to BCS class II, showing low solubility and high permeability with a moderate F value (&lt;49%). Recently, FBX\/L-pyroglutamic acid cocrystal (FBX-PG) was developed with an improving 4-fold increase of FBX solubility. Nevertheless, the in vivo pharmacokinetic properties of FBX-PG have not been evaluated yet. Therefore, the pharmacokinetic feasibility of FBX in FBX- and FBX-PG-treated rats and mice was compared in this study. The results showed that the bioavailability (F) values of FBX were 210% and 159% in FBX-PG-treated rats and mice, respectively. The 2.10-fold greater total area under the plasma concentration\u2013time curve from time zero to infinity (AUC0-inf) of FBX was due to the increased absorption [i.e., 2.60-fold higher the first peak plasma concentration (Cmax,1) at 15 min] and entero-hepatic circulation of FBX [i.e., 1.68-fold higher the second peak plasma concentration (Cmax,2) at 600 min] in FBX-PG-treated rats compared to the FBX-treated rats. The 1.59-fold greater AUC0-inf of FBX was due to a 1.65-fold higher Cmax,1 at 5 min, and a 1.15-fold higher Cmax,2 at 720 min of FBX in FBX-PG-treated mice compared to those in FBX-treated mice. FBX was highly distributed in the liver, stomach, small intestine, and lungs in both groups of mice, and the FBX distributions to the liver and lungs were increased in FBX-PG-treated mice compared to FBX-treated mice. The results suggest the FBX-PG has a suitable pharmacokinetic profile of FBX for improving its oral F value.<\/jats:p>","DOI":"10.3390\/pharmaceutics15082167","type":"journal-article","created":{"date-parts":[[2023,8,21]],"date-time":"2023-08-21T08:53:31Z","timestamp":1692608011000},"page":"2167","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Evaluation of Pharmacokinetic Feasibility of Febuxostat\/L-pyroglutamic Acid Cocrystals in Rats and Mice"],"prefix":"10.3390","volume":"15","author":[{"given":"Jeong-Eun","family":"Yu","sequence":"first","affiliation":[{"name":"College of Pharmacy and Integrated Research Institute for Drug Development, Dongguk University_Seoul, 32 Dongguk-ro, Ilsandong-gu, Goyang-si 10326, Gyeonggi-do, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Byoung Hoon","family":"You","sequence":"additional","affiliation":[{"name":"College of Pharmacy and Integrated Research Institute for Drug Development, Dongguk University_Seoul, 32 Dongguk-ro, Ilsandong-gu, Goyang-si 10326, Gyeonggi-do, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingoo","family":"Bae","sequence":"additional","affiliation":[{"name":"College of Pharmacy and Integrated Research Institute for Drug Development, Dongguk University_Seoul, 32 Dongguk-ro, Ilsandong-gu, Goyang-si 10326, Gyeonggi-do, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seung Yon","family":"Han","sequence":"additional","affiliation":[{"name":"College of Pharmacy and Integrated Research Institute for Drug Development, Dongguk University_Seoul, 32 Dongguk-ro, Ilsandong-gu, Goyang-si 10326, Gyeonggi-do, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiwon","family":"Jung","sequence":"additional","affiliation":[{"name":"College of Pharmacy, CHA University, 335 Pangyo-ro, Bundang-gu, Seongnam-si 13488, Gyeonggi-do, Republic of Korea"},{"name":"Oncobix Co., Ltd., 120 Heungdeokjungang-ro, Giheung-gu, Yongin-si 16950, Gyeonggi-do, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9360-6436","authenticated-orcid":false,"given":"Young Hee","family":"Choi","sequence":"additional","affiliation":[{"name":"College of Pharmacy and Integrated Research Institute for Drug Development, Dongguk University_Seoul, 32 Dongguk-ro, Ilsandong-gu, Goyang-si 10326, Gyeonggi-do, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3188","DOI":"10.1021\/cg400583z","article-title":"Soluble cocrystals of the xanthine oxidase inhibitor febuxostat","volume":"13","author":"Maddileti","year":"2013","journal-title":"Cryst. Growth Des."},{"key":"ref_2","first-page":"622","article-title":"Lamotrigine novel cocrystals: An attempt to enhance physicochemical parameters","volume":"13","author":"Samineni","year":"2022","journal-title":"J. Pharm. Negat."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1002\/jps.20578","article-title":"Pharmaceutical co-crystals","volume":"95","author":"Vishweshwar","year":"2006","journal-title":"J. Pharm. Sci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2537","DOI":"10.1016\/j.apsb.2021.03.030","article-title":"Pharmaceutical cocrystals: A review of preparations, physicochemical properties and applications","volume":"11","author":"Guo","year":"2021","journal-title":"Acta. Pharm. Sin. B."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"6370","DOI":"10.1021\/acs.cgd.8b00933","article-title":"Creating cocrystals: A review of pharmaceutical cocrystal preparation routes and applications","volume":"18","author":"Maryam","year":"2018","journal-title":"Cryst. Growth Des."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Ronik, D.F.V., Hosni, A.P., Brancalione, R.C., Biscaia, I.F.B., Bernardi, L.S., and Oliveira, P.R. (2023). Synthesis and characterization of ezetimibe pharmaceutical cocrystal: A reaction crystallization method to improve physicochemical properties and hypolipemic activity evaluation. J. Braz. Chem. Soc., e-20230114.","DOI":"10.21577\/0103-5053.20230114"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"106530","DOI":"10.1016\/j.ejps.2023.106530","article-title":"Preparation of pazopanib-fumarate disodium glycyrrhizinate nanocrystalline micelles by liquid-assisted ball milling","volume":"188","author":"Shen","year":"2023","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_8","first-page":"734","article-title":"Exploring cocrystals of imatinib: Synthesis, characterization, and in vitro evaluation","volume":"10","author":"Shubham","year":"2023","journal-title":"J. Surv. Fish. Sci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2923","DOI":"10.1021\/acs.cgd.6b00266","article-title":"Improving the solubility and bioavailability of apixaban via apixaban\u2013oxalic acid cocrystal","volume":"16","author":"Chen","year":"2016","journal-title":"Cryst. Growth Des."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1560","DOI":"10.1111\/j.2042-7158.2010.01189.x","article-title":"Bioavailability of indomethacin-saccharin cocrystals","volume":"62","author":"Jung","year":"2010","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Zhang, L., Kong, D., Wang, H., Jiao, L., Zhao, X., Song, J., Yang, D., Yang, H., Yang, S., and Du, G. (2021). Cocrystal of apixaban\u2013quercetin: Improving solubility and bioavailability of drug combination of two poorly soluble drugs. Molecules, 26.","DOI":"10.3390\/molecules26092677"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1111\/j.1365-2125.2007.03016.x","article-title":"Effect of food or antacid on pharmacokinetics and pharmacodynamics of febuxostat in healthy subjects","volume":"65","author":"Khosravan","year":"2008","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"3004","DOI":"10.1001\/jama.1991.03470210072035","article-title":"Incidence and risk factors for gout in white men","volume":"266","author":"Roubenoff","year":"1991","journal-title":"JAMA"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1007\/s40005-019-00464-w","article-title":"Febuxostat loaded \u03b2-cyclodextrin based nanosponge tablet: An in vitro and in vivo evaluation","volume":"50","author":"Amin","year":"2019","journal-title":"J. Pharm. Investig."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1200","DOI":"10.1056\/NEJMoa1710895","article-title":"Cardiovascular safety of febuxostat or allopurinol in patients with gout","volume":"378","author":"White","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1111\/jcpt.13285","article-title":"Development of LC-MS\/MS determination method and backpropagation artificial neural networks pharmacokinetic model of febuxostat in healthy subjects","volume":"46","author":"Xu","year":"2021","journal-title":"J. Clin. Pharm. Ther."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1016\/j.ijpharm.2014.12.003","article-title":"Formulation, optimization and in vitro-in vivo evaluation of febuxostat nanosuspension","volume":"478","author":"Ahuja","year":"2015","journal-title":"Int. J. Pharm."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"An, J.-H., Lim, C., Ryu, H.C., Kim, J.S., Kim, H.M., Kiyonga, A.N., Park, M., Suh, Y.G., Park, G.H., and Jung, K. (2017). Structural characterization of febuxostat\/L-pyroglutamic acid cocrystal using solid-state 13C-NMR and investigational study of its water solubility. Crystals, 7.","DOI":"10.3390\/cryst7120365"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e15404","DOI":"10.1016\/j.heliyon.2023.e15404","article-title":"Quality-by-design based fabrication of febuxostat-loaded nanoemulsion: Statistical optimization, characterizations, permeability, and bioavailability studies","volume":"9","author":"Gurumukhi","year":"2023","journal-title":"Heliyon"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1321","DOI":"10.1080\/10717544.2021.1927247","article-title":"Formulation, characterization, optimization, and in-vivo performance of febuxostat self-nano-emulsifying system loaded sublingual films","volume":"28","author":"Habib","year":"2021","journal-title":"Drug. Deliv."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Haq, N., Alghaith, A.F., Alshehri, S., and Shakeel, F. (2022). Solubility and thermodynamic data of febuxostat in various mono solvents at different temperatures. Molecules, 27.","DOI":"10.3390\/molecules27134043"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"3834368","DOI":"10.1155\/2021\/3834368","article-title":"Cocrystallization of febuxostat with pyridine coformers: Crystal structural and physicochemical properties analysis","volume":"2021","author":"Gao","year":"2021","journal-title":"J Chem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1016\/j.ajps.2016.05.009","article-title":"Preparation, optimization and in vitro\u2013in vivo investigation for capsules of the choline salt of febuxostat","volume":"11","author":"Han","year":"2016","journal-title":"Asian J. Pharm. Sci."},{"key":"ref_24","first-page":"480","article-title":"Syntheses, structure characterization and dissolution of two novel cocrystals of febuxostat","volume":"15","author":"Kang","year":"2016","journal-title":"Mol. Struct."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"101724","DOI":"10.1016\/j.jsps.2023.101724","article-title":"Development and evaluation of febuxostat solid dispersion through screening method","volume":"31","author":"Sohn","year":"2023","journal-title":"Saudi Pharm. J."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2299","DOI":"10.1021\/cg050125l","article-title":"Saccharin salts of active pharmaceutical ingredients, their crystal structures, and increased water solubilities","volume":"5","author":"Banerjee","year":"2005","journal-title":"Cryst. Growth Des."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2699","DOI":"10.1021\/cg060327x","article-title":"Pharmaceutical cocrystal and salts of norfloxacin","volume":"6","author":"Basavoju","year":"2006","journal-title":"Cryst. Growth Des."},{"key":"ref_28","unstructured":"Byrn, S.R., Pfeiffer, R.R., and Stowell, J.G. (1999). Solid-State Chemistry of Drugs, SSCI. [2nd ed.]."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2252","DOI":"10.1021\/cg801039j","article-title":"Solubility advantage of pharmaceutical cocrystals","volume":"9","author":"Good","year":"2009","journal-title":"Cryst. Growth Des."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1888","DOI":"10.1007\/s11095-006-9032-3","article-title":"Use of a glutaric acid cocrystal to improve oral bioavailability of a low solubility API","volume":"23","author":"McNamara","year":"2006","journal-title":"Pharm. Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"8456","DOI":"10.1021\/ja035776p","article-title":"Crystal engineering of novel cocrystals of a triazole drug with 1,4-dicarboxylic acids","volume":"125","author":"Remenar","year":"2003","journal-title":"J. Am. Chem. Soc."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"4135","DOI":"10.1021\/cg200704s","article-title":"Fast dissolving curcumin cocrystals","volume":"11","author":"Sanphui","year":"2011","journal-title":"Cryst. Growth Des."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"5013","DOI":"10.1039\/c1cc10204d","article-title":"New polymorphs of curcumin","volume":"47","author":"Sanphui","year":"2011","journal-title":"Chem. Commun."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1208\/s12249-021-02182-9","article-title":"Novel co-crystals and eutectics of febuxostat: Characterization, mechanism of formation, and improved dissolution","volume":"23","author":"Jagia","year":"2021","journal-title":"AAPS PharmSciTech."},{"key":"ref_35","unstructured":"(2018, May 03). Safety Data Sheet (L-pyroglutamic Acid) Spectrum Chemical Home Page. Available online: https:\/\/www.spectrumchemical.com\/media\/sds\/P1835_AGHS.pdf."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1021\/cg101556s","article-title":"Pharmaceutical Crystallization","volume":"11","author":"Chen","year":"2011","journal-title":"Cryst. Growth Des."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1016\/j.ejpb.2016.11.034","article-title":"Food, gastrointestinal pH, and models of oral drug absorption","volume":"112","author":"Abuhelwa","year":"2017","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_38","unstructured":"Ryu, H.C. (2015). Crystalline Febuxostat Pidolate Salt and Method for Preparing Thereof. (10-1501253), K.R. Patent."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"111892","DOI":"10.1016\/j.jep.2019.111892","article-title":"Lonicera japonica extract increases metformin distribution in the liver without change of systemic exposed metformin in rats","volume":"238","author":"Han","year":"2019","journal-title":"J. Ethnopharmacol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1004","DOI":"10.1002\/ptr.6036","article-title":"Houttuynia cordata extract increased systemic exposure and liver concentrations of metformin through OCTs and MATEs in rats","volume":"32","author":"You","year":"2018","journal-title":"Phytother. Res."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"You, B.H., Bae, M., Han, S.Y., Jung, J., Jung, K., and Choi, Y.H. (2023). Pharmacokinetic feasibility of stability-enhanced solid-state (SESS) tenofovir disoproxil free base crystal. Pharmaceutics, 15.","DOI":"10.3390\/pharmaceutics15051392"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1002\/jat.727","article-title":"A good practice guide to the administration of substances and removal of blood, including routes and volumes","volume":"21","author":"Diehl","year":"2001","journal-title":"J. Appl. Toxicol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1038\/laban1005-39","article-title":"A rapid, simple, and humane method for submandibular bleeding of mice using a lancet","volume":"34","author":"Golde","year":"2005","journal-title":"Lab. Anim."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1148155","DOI":"10.3389\/fphar.2023.1148155","article-title":"Change of metformin concentrations in the liver as a pharmacological target site of metformin after long-term combined treatment with ginseng berry extract","volume":"14","author":"Lee","year":"2023","journal-title":"Front. Pharmacol."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Han, S.Y., You, B.H., Kim, Y.C., Chin, Y.-W., and Choi, Y.H. (2015). Dose-independent ADME properties and tentative identification of metabolites of \u03b1-mangostin from Garcinia mangostana in mice by automated microsampling and UPLC-MS\/MS methods. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0131587"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1248\/bpb.b14-00524","article-title":"Pharmacokinetics, tissue distribution, and tentative metabolite identification of sauchinone in mice by microsampling and HPLC-MS\/MS methods","volume":"38","author":"Kim","year":"2015","journal-title":"Biol. Pharm. Bull."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Gibaldi, M., and Perrier, D. (1982). Pharmacokinetics, Marcel-Dekker. [2nd ed.].","DOI":"10.1201\/b14095"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1007\/BF01059061","article-title":"Evaluation of potential causes for the incomplete bioavailability of furosemide: Gastric first-pass metabolism","volume":"11","author":"Lee","year":"1983","journal-title":"J. Pharmacokinet. Biopharm."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1177\/0091270010365549","article-title":"Metabolism and excretion of [14C] febuxostat, a novel nonpurine selective inhibitor of xanthine oxidase, in healthy male subjects","volume":"51","author":"Grabowski","year":"2011","journal-title":"J. Clin. Pharmacol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"821","DOI":"10.2165\/00003088-200645080-00005","article-title":"Pharmacokinetics, pharmacodynamics and safety of febuxostat, a non-purine selective inhibitor of xanthine oxidase, in a dose escalation study in healthy subjects","volume":"45","author":"Khosravan","year":"2006","journal-title":"Clin. Pharmacokinet."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1038\/nrd4309","article-title":"Lessons learned from the fate of AstraZeneca\u2019s drug pipeline: A five-dimensional framework","volume":"13","author":"Cook","year":"2014","journal-title":"Nat. Rev. Drug. Discov."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"39","DOI":"10.2174\/138920006774832578","article-title":"Tissue distribution and pharmacodynamics: A complicated relationship","volume":"7","author":"Lin","year":"2006","journal-title":"Curr. Drug. Metab."},{"key":"ref_53","first-page":"207","article-title":"The mighty mouse: The impact of rodents on advances in biomedical research","volume":"110","author":"Bryda","year":"2013","journal-title":"Mo. Med."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1","DOI":"10.51847\/mixPbfZddp","article-title":"Animals used in experimental pharmacology and 3 Rs","volume":"12","author":"Sivakrishnan","year":"2021","journal-title":"Pharmacophore"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1208\/s12248-012-9344-7","article-title":"A Physiologically based pharmacokinetic model of mitoxantrone in mice and scale-up to humans: A semi-mechanistic model incorporating DNA and protein binding","volume":"14","author":"An","year":"2012","journal-title":"AAPS J."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/j.fct.2014.01.028","article-title":"Absorption, tissue distribution, tissue metabolism and safety of \u03b1-mangostin in mangosteen extract using mouse models","volume":"66","author":"Choi","year":"2014","journal-title":"Food Chem. Toxicol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"718","DOI":"10.1016\/0041-008X(70)90077-3","article-title":"Increased ethanol toxicity in old rats: Changes in LD50, in vivo and in vitro metabolism, and liver alcohol dehydrogenase activity","volume":"16","author":"Wiberg","year":"1970","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_58","unstructured":"(2011, August 21). The International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) Home Page. Available online: https:\/\/database.ich.org\/sites\/default\/files\/ICH_Q3C-R8_Guideline_Step4_2021_0422_1.pdf."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1016\/0091-3057(93)90266-V","article-title":"Tolerance to effects of high doses of ethanol: 1. Lethal effects in mice","volume":"45","author":"Tsibulsky","year":"1993","journal-title":"Pharmacol. Biochem. Behav."},{"key":"ref_60","first-page":"51881","article-title":"Catheterization of the carotid artery and jugular vein to perform hemodynamic measures, infusions and blood sampling in a conscious rat model","volume":"95","author":"Feng","year":"2015","journal-title":"J. Vis. Exp."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.exphem.2015.10.008","article-title":"Bleeding the laboratory mouse: Not all methods are equal","volume":"44","author":"Hoggatt","year":"2016","journal-title":"Exp. Hematol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"87","DOI":"10.4103\/0976-500X.72350","article-title":"Blood sample collection in small laboratory animals","volume":"1","author":"Parasuraman","year":"2010","journal-title":"J. Pharmacol. Pharmacother."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Arunachalam, K., and Sasidharan, S.P. (2021). Bioassays in Experimental and Preclinical Pharmacology, Springer. [1st ed.].","DOI":"10.1007\/978-1-0716-1233-0"},{"key":"ref_64","unstructured":"Florida Atlantic University Institutional Animal Care and Use Committee (FAU IACUC) (2021). Guidelines for Rodent Survival Blood Collection, Florida Atlantic University."},{"key":"ref_65","first-page":"47","article-title":"Methods of blood collection in the mouse","volume":"29","author":"Wolforth","year":"2000","journal-title":"Lab. Anim."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Bhalani, D.V., Nutan, B., Kumar, A., and Singh Chandel, A.K. (2022). Bioavailability enhancement techniques for poorly aqueous soluble drugs and therapeutics. Biomedicines, 10.","DOI":"10.3390\/biomedicines10092055"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Liu, Y., Yang, F., Zhao, X., Wang, S., Yang, Q., and Zhang, X. (2022). Crystal structure, solubility, and pharmacokinetic study on a hesperetin cocrystal with piperine as conformer. Pharmaceutics, 14.","DOI":"10.3390\/pharmaceutics14010094"},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Kimoto, K., Yamamoto, M., Karashima, M., Hohokabe, M., Takeda, J., Yamamoto, K., and Ikeda, Y. (2020). Pharmaceutical cocrystal development of TAK-020 with enhanced oral absorption. Crystals, 10.","DOI":"10.3390\/cryst10030211"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"4122","DOI":"10.1021\/acs.molpharmaceut.1c00537","article-title":"In vitro-In vivo correlation in cocrystal dissolution: Consideration of drug release profiles based on coformer dissolution and absorption behavior","volume":"18","author":"Kataoka","year":"2021","journal-title":"Mol. Pharm."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1080\/00498250801956350","article-title":"In vitro drug-drug interaction studies with febuxostat, a novel non-purine selective inhibitor of xanthine oxidase: Plasma protein binding, identification of metabolic enzymes and cytochrome P450 inhibition","volume":"38","author":"Mukoyoshi","year":"2008","journal-title":"Xenobiotica"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1007\/s40262-016-0466-4","article-title":"Clinical pharmacokinetics and pharmacodynamics of febuxostat","volume":"56","author":"Kamel","year":"2017","journal-title":"Clin. Pharmacokinet."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"351","DOI":"10.2165\/11319320-000000000-00000","article-title":"Multiple peaking phenomena in pharmacokinetic disposition","volume":"49","author":"Davies","year":"2010","journal-title":"Clin. Pharmacokinet."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1002\/bdd.1843","article-title":"Therapeutic drug monitoring and pharmacokinetic compartmental analysis of sulpiride double-peak absorption profile after oral administration to human volunteers","volume":"34","author":"Helmy","year":"2013","journal-title":"Biopharm. Drug Dispos."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1208\/s12248-014-9693-5","article-title":"Empirical and semi-mechanistic modelling of double-peaked pharmacokinetic profile phenomenon due to gastric emptying","volume":"17","author":"Ogungbenro","year":"2015","journal-title":"AAPS J."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1046\/j.1365-2885.2002.00418.x","article-title":"Distribution of orally administered trimethoprim and sulfadiazine into noninfected subcutaneous tissue chambers in adult ponies","volume":"25","author":"Ensink","year":"2002","journal-title":"J. Vet. Pharmacol. Ther."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1055\/a-1321-1519","article-title":"Pharmacokinetic properties of moracin C in mice","volume":"87","author":"You","year":"2021","journal-title":"Planta Med."}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/15\/8\/2167\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:38:41Z","timestamp":1760128721000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/15\/8\/2167"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8,21]]},"references-count":76,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2023,8]]}},"alternative-id":["pharmaceutics15082167"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics15082167","relation":{},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,8,21]]}}}