{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,4]],"date-time":"2025-07-04T00:40:03Z","timestamp":1751589603567,"version":"3.41.0"},"reference-count":36,"publisher":"Springer Science and Business Media LLC","issue":"7","license":[{"start":{"date-parts":[[2018,4,27]],"date-time":"2018-04-27T00:00:00Z","timestamp":1524787200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Pharm Res"],"published-print":{"date-parts":[[2018,7]]},"DOI":"10.1007\/s11095-018-2402-9","type":"journal-article","created":{"date-parts":[[2018,4,27]],"date-time":"2018-04-27T15:42:23Z","timestamp":1524843743000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Population Pharmacokinetic Modeling to Describe the Total Plasma and Free Brain Levels of Fluconazole in Healthy and Cryptococcus neoformans Infected Rats: How Does the Infection Impact the Drug\u2019s Levels on Biophase?"],"prefix":"10.1007","volume":"35","author":[{"given":"Izabel Almeida","family":"Alves","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keli Jaqueline","family":"Staudt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fernando Olinto","family":"Carre\u00f1o","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Graziela","family":"de Araujo Lock","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carolina","family":"de Miranda Silva","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stela Maris Kuze","family":"Rates","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Teresa","family":"Dalla Costa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bibiana Verlindo","family":"De Araujo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2018,4,27]]},"reference":[{"key":"2402_CR1","doi-asserted-by":"publisher","first-page":"183","DOI":"10.7326\/0003-4819-113-3-183","volume":"113","author":"RA Larsen","year":"1990","unstructured":"Larsen RA, Leal ME, Chan LS. Fluconazole compared with amphotericin b plus flucytosine for cryptococcal meningitis in aids: a randomized trial. Ann Intern Med. 1990;113:183\u20137.","journal-title":"Ann Intern Med"},{"key":"2402_CR2","doi-asserted-by":"publisher","first-page":"126","DOI":"10.1056\/NEJM197907193010303","volume":"301","author":"JE Bennett","year":"1979","unstructured":"Bennett JE, Dismukes WE, Duma RJ, Medoff G, Sande MA, Gallis H, et al. A comparison of amphotericin B alone and combined with flucytosine in the treatment of cryptoccal meningitis. N Engl J Med. 1979;301:126\u201331.","journal-title":"N Engl J Med"},{"key":"2402_CR3","doi-asserted-by":"publisher","first-page":"169","DOI":"10.2147\/CLEP.S38850","volume":"6","author":"DJ Sloan","year":"2014","unstructured":"Sloan DJ, Parris V. Cryptococcal meningitis: epidemiology and therapeutic options. J Clin Epidemiol. 2014;6:169\u201382.","journal-title":"J Clin Epidemiol"},{"key":"2402_CR4","doi-asserted-by":"publisher","first-page":"455","DOI":"10.1097\/QCO.0b013e32832fa214","volume":"22","author":"DJ Sloan","year":"2009","unstructured":"Sloan DJ, Dedicoat MJ, Lalloo DG. Treatment of Cryptococcal meningitis in resource limited settings. Curr Opin Infect Dis. 2009;22:455\u201363.","journal-title":"Curr Opin Infect Dis"},{"key":"2402_CR5","doi-asserted-by":"publisher","first-page":"2435","DOI":"10.1093\/jac\/dkt221","volume":"68","author":"A Loyse","year":"2013","unstructured":"Loyse A, Dromer F, Day J, Lortholary O, Harrison TS. Flucytosine and cryptococcosis: time to urgently address the worldwide accessibility of a 50-year-old antifungal. J Antimicrob Chemother. 2013;68:2435\u201344.","journal-title":"J Antimicrob Chemother"},{"key":"2402_CR6","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1055\/s-0034-1372342","volume":"34","author":"AT Makadzange","year":"2014","unstructured":"Makadzange AT, McHugh G. New approaches to the diagnosis and treatment of cryptococcal meningitis. Semin Neurol. 2014;34:47\u201360.","journal-title":"Semin Neurol"},{"key":"2402_CR7","doi-asserted-by":"publisher","first-page":"198","DOI":"10.1055\/s-2008-1063858","volume":"29","author":"DI Zonios","year":"2008","unstructured":"Zonios DI, Bennett JE. Update on azole antifungals. Semin Respir Crit Care Med. 2008;29:198\u2013210.","journal-title":"Semin Respir Crit Care Med"},{"key":"2402_CR8","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1007\/s002280100301","volume":"57","author":"C Joukhadar","year":"2001","unstructured":"Joukhadar C, Derendorf H, M\u00fcller M, Microdialysis. A novel tool for clinical studies of anti-infective agents. Eur J Clin Pharmacol. 2001;57:211\u20139.","journal-title":"Eur J Clin Pharmacol"},{"key":"2402_CR9","doi-asserted-by":"publisher","first-page":"338","DOI":"10.1016\/S1369-5274(03)00081-X","volume":"6","author":"L Romani","year":"2003","unstructured":"Romani L, Bistoni F, Puccetti P. Adaptation of Candida albicans to the host environment: the role of morphogenesis in virulence and survival in mammalian hosts. Curr Opin Microbiol. 2003;6:338\u201343.","journal-title":"Curr Opin Microbiol"},{"key":"2402_CR10","doi-asserted-by":"publisher","first-page":"2793","DOI":"10.1128\/AAC.00216-13","volume":"57","author":"A Sudan","year":"2013","unstructured":"Sudan A, Livermore J, Howard SJ, Al-Nakeeb Z, Sharp A, Goodwin J, et al. Pharmacokinetics and pharmacodynamics of fluconazole for cryptococcal meningoencephalitis: implications for antifungal therapy and in vitro susceptibility breakpoints. Antimicrob Agents Chemother. 2013;57:2793\u2013800.","journal-title":"Antimicrob Agents Chemother"},{"key":"2402_CR11","doi-asserted-by":"publisher","first-page":"e00321","DOI":"10.1128\/AAC.00321-17","volume":"61","author":"IA Alves","year":"2017","unstructured":"Alves IA, Staudt KJ, Silva C de M, Lock G de A, Dalla Costa T, de Araujo BV. Influence of experimental Cryptococcal meningitis in Wistar rats on Voriconazole brain penetration assessed by microdialysis. Antimicrob Agents Chemother. 2017;61:e00321\u201317.","journal-title":"Antimicrob Agents Chemother"},{"key":"2402_CR12","unstructured":"Paxinos G, Watson C. The rat brain in stereotaxic coordinates: hard cover edition: Academic Press; 2006."},{"key":"2402_CR13","doi-asserted-by":"publisher","first-page":"5852","DOI":"10.1128\/AAC.01323-12","volume":"56","author":"FJ Azeredo","year":"2012","unstructured":"Azeredo FJ, de Ara\u00fajo BV, Haas SE, Torres B, Pigatto M, de Andrade C, et al. Comparison of fluconazole renal penetration levels in healthy and Candida albicans-infected Wistar rats. Antimicrob Agents Chemother. 2012;56:5852\u20137.","journal-title":"Antimicrob Agents Chemother"},{"key":"2402_CR14","doi-asserted-by":"publisher","first-page":"461","DOI":"10.5935\/0100-4042.20140082","volume":"37","author":"BGS Torres","year":"2014","unstructured":"Torres BGS, Uch\u00f4a FDT, Canto RFS, Crestani A, Eifler-Lima V, Costa TD. Bioanalytical method for the quantification of the monastrol derivative anticancer candidate lasom 65 in pre-clinical pharmacokinetic investigations. Qu\u00edm Nova. 2014;37:461\u20134.","journal-title":"Qu\u00edm Nova."},{"key":"2402_CR15","doi-asserted-by":"publisher","first-page":"5898","DOI":"10.1128\/AAC.01115-12","volume":"56","author":"A Espinel-Ingroff","year":"2012","unstructured":"Espinel-Ingroff A, Aller AI, Canton E, Casta\u00f1\u00f3n-Olivares LR, Chowdhary A, Cordoba S, et al. Cryptococcus neoformans-Cryptococcus gattii species complex: an international study of wild-type susceptibility endpoint distributions and epidemiological cutoff values for fluconazole, Itraconazole, Posaconazole, and Voriconazole. Antimicrob Agents Chemother. 2012;56:5898\u2013906.","journal-title":"Antimicrob Agents Chemother"},{"key":"2402_CR16","doi-asserted-by":"publisher","first-page":"693","DOI":"10.1177\/009286159803200310","volume":"32","author":"SE Tett","year":"1998","unstructured":"Tett SE, Holford NHG, McLachlan AJ. Population pharmacokinetics and pharmacodynamics: an underutilized resource. Drug Inf J. 1998;32:693\u2013710.","journal-title":"Drug Inf J"},{"key":"2402_CR17","doi-asserted-by":"publisher","first-page":"1570","DOI":"10.1023\/A:1016048100712","volume":"13","author":"H Yang","year":"1996","unstructured":"Yang H, Wang Q, Elmquist WF. Fluconazole distribution to the brain: a crossover study in freely-moving rats using in vivo microdialysis. Pharm Res. 1996;13:1570\u20135.","journal-title":"Pharm Res"},{"key":"2402_CR18","doi-asserted-by":"publisher","first-page":"3314","DOI":"10.1002\/jps.24552","volume":"104","author":"FJ Azeredo","year":"2015","unstructured":"Azeredo FJ, Hass SE, Sansone P, Derendorf H, Costa TD, De Araujo BV. Does the anesthetic urethane influence the pharmacokinetics of antifungal drugs? A population pharmacokinetic investigation in rats. J Pharm Sci. 2015;104:3314\u20138.","journal-title":"J Pharm Sci"},{"key":"2402_CR19","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1086\/649858","volume":"50","author":"JR Perfect","year":"2010","unstructured":"Perfect JR, Dismukes WE, Dromer F, Goldman DL, Graybill JR, Hamill RJ, et al. Clinical practice guidelines for the Management of Cryptococcal Disease: 2010 update by the Infectious Diseases Society of America. Clin Infect Dis. 2010;50:291\u2013322.","journal-title":"Clin Infect Dis"},{"key":"2402_CR20","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1056\/NEJM199401273300407","volume":"330","author":"JA Como","year":"1994","unstructured":"Como JA, Dismukes WE. Oral azole drugs as systemic antifungal therapy. N Engl J Med. 1994;330:263\u201372.","journal-title":"N Engl J Med"},{"key":"2402_CR21","doi-asserted-by":"publisher","first-page":"196","DOI":"10.1111\/j.2042-7158.1994.tb03777.x","volume":"46","author":"SG Jezequel","year":"1994","unstructured":"Jezequel SG. Fluconazole: interspecies scaling and allometric relationships of pharmacokinetic properties. J Pharm Pharmacol. 1994;46:196\u20139.","journal-title":"J Pharm Pharmacol"},{"key":"2402_CR22","doi-asserted-by":"publisher","first-page":"770","DOI":"10.1002\/jps.20290","volume":"94","author":"F-X Mathy","year":"2005","unstructured":"Mathy F-X, Ntivunwa D, Verbeeck RK, Pr\u00e9at V. Fluconazole distribution in rat dermis following intravenous and topical application: a microdialysis study. J Pharm Sci. 2005;94:770\u201380.","journal-title":"J Pharm Sci"},{"key":"2402_CR23","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1590\/S0100-40422007000100029","volume":"30","author":"DG Pereira","year":"2007","unstructured":"Pereira DG. The importance of metabolism in drug design. Qu\u00edm Nova. 2007;30:171\u20137.","journal-title":"Qu\u00edm Nova"},{"key":"2402_CR24","doi-asserted-by":"publisher","first-page":"160","DOI":"10.1128\/AAC.46.1.160-165.2002","volume":"46","author":"E Wang","year":"2002","unstructured":"Wang E, Lew K, Casciano CN, Clement RP, Johnson WW. Interaction of common azole antifungals with P glycoprotein. Antimicrob Agents Chemother. 2002;46:160\u20135.","journal-title":"Antimicrob Agents Chemother"},{"key":"2402_CR25","doi-asserted-by":"publisher","first-page":"573","DOI":"10.1517\/17425255.3.4.573","volume":"3","author":"S Kethireddy","year":"2007","unstructured":"Kethireddy S, Andes D. CNS pharmacokinetics of antifungal agents. Expert Opin Drug Metab Toxicol. 2007;3:573\u201381.","journal-title":"Expert Opin Drug Metab Toxicol"},{"key":"2402_CR26","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1124\/jpet.102.037549","volume":"303","author":"K Yasuda","year":"2002","unstructured":"Yasuda K, Lan L-B, Sanglard D, Furuya K, Schuetz JD, Schuetz EG. Interaction of cytochrome P450 3A inhibitors with P-glycoprotein. J Pharmacol Exp Ther. 2002;303:323\u201332.","journal-title":"J Pharmacol Exp Ther"},{"key":"2402_CR27","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/S0090-9556(24)15274-9","volume":"27","author":"MA Gibbs","year":"1999","unstructured":"Gibbs MA, Thummel KE, Shen DD, Kunze KL. Inhibition of cytochrome P-450 3A (CYP3A) in human intestinal and liver Microsomes: comparison of K i values and impact of CYP3A5 expression. Drug Metab Dispos. 1999;27:180\u20137.","journal-title":"Drug Metab Dispos"},{"key":"2402_CR28","doi-asserted-by":"publisher","first-page":"2274","DOI":"10.1007\/s11064-017-2240-x","volume":"42","author":"W Wang","year":"2017","unstructured":"Wang W, Zheng N, Zhang J, Huang X, Yu S. Effect of efflux transporter inhibition on the distribution of fluconazole in the rat brain. Neurochem Res. 2017;42:2274\u201381.","journal-title":"Neurochem Res"},{"key":"2402_CR29","doi-asserted-by":"publisher","first-page":"4985","DOI":"10.1128\/IAI.72.9.4985-4995.2004","volume":"72","author":"YC Chang","year":"2004","unstructured":"Chang YC, Stins MF, McCaffery MJ, Miller GF, Pare DR, Dam T, et al. Cryptococcal yeast cells invade the central nervous system via transcellular penetration of the blood-brain barrier. Infect Immun. 2004;72:4985\u201395.","journal-title":"Infect Immun"},{"key":"2402_CR30","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1177\/0300060513504365","volume":"42","author":"C-Y Xu","year":"2014","unstructured":"Xu C-Y, Zhu H-M, Wu J-H, Wen H, Liu C-J. Increased permeability of blood-brain barrier is mediated by serine protease during Cryptococcus meningitis. J Int Med Res. 2014;42:85\u201392.","journal-title":"J Int Med Res"},{"key":"2402_CR31","doi-asserted-by":"publisher","first-page":"648","DOI":"10.1128\/AAC.28.5.648","volume":"28","author":"MJ Humphrey","year":"1985","unstructured":"Humphrey MJ, Jevons S, Tarbit MH. Pharmacokinetic evaluation of UK-49,858, a metabolically stable triazole antifungal drug, in animals and humans. Antimicrob Agents Chemother. 1985;28:648\u201353.","journal-title":"Antimicrob Agents Chemother"},{"key":"2402_CR32","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1517\/17425255.2013.741589","volume":"9","author":"X Chu","year":"2013","unstructured":"Chu X, Bleasby K, Evers R. Species differences in drug transporters and implications for translating preclinical findings to humans. Expert Opin Drug Metab Toxicol. 2013;9:237\u201352.","journal-title":"Expert Opin Drug Metab Toxicol"},{"key":"2402_CR33","doi-asserted-by":"publisher","first-page":"963","DOI":"10.1080\/00498250600861751","volume":"36","author":"K Bleasby","year":"2006","unstructured":"Bleasby K, Castle JC, Roberts CJ, Cheng C, Bailey WJ, Sina JF, et al. Expression profiles of 50 xenobiotic transporter genes in humans and pre-clinical species: a resource for investigations into drug disposition. Xenobiotica. 2006;36:963\u201388.","journal-title":"Xenobiotica"},{"key":"2402_CR34","doi-asserted-by":"publisher","first-page":"363","DOI":"10.1002\/j.1552-4604.1988.tb03159.x","volume":"28","author":"G Foulds","year":"1988","unstructured":"Foulds G, Brennan DR, Wajszczuk C, Catanzaro A, Garg DC, Knopf W, et al. Fluconazole penetration into cerebrospinal fluid in humans. J Clin Pharmacol. 1988;28:363\u20136.","journal-title":"J Clin Pharmacol"},{"key":"2402_CR35","doi-asserted-by":"publisher","first-page":"1556","DOI":"10.1086\/593194","volume":"47","author":"N Longley","year":"2008","unstructured":"Longley N, Muzoora C, Taseera K, Mwesigye J, Rwebembera J, Chakera A, et al. Dose response effect of high-dose fluconazole for HIV-associated cryptococcal meningitis in southwestern Uganda. Clin Infect Dis Off Publ Infect Dis Soc Am. 2008;47:1556\u201361.","journal-title":"Clin Infect Dis Off Publ Infect Dis Soc Am"},{"key":"2402_CR36","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1080\/13693780701851695","volume":"46","author":"E Milefchik","year":"2008","unstructured":"Milefchik E, Ann Leal M, Haubrich R, Bozzette SA, Tilles JG, Leedom JM, et al. Fluconazole alone or combined with flucytosine for the treatment of AIDS-associated cryptococcal meningitis. Med Mycol. 2008;46:393\u20135.","journal-title":"Med Mycol"}],"container-title":["Pharmaceutical Research"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/article\/10.1007\/s11095-018-2402-9\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s11095-018-2402-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s11095-018-2402-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,3]],"date-time":"2025-07-03T23:58:34Z","timestamp":1751587114000},"score":1,"resource":{"primary":{"URL":"http:\/\/link.springer.com\/10.1007\/s11095-018-2402-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,4,27]]},"references-count":36,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2018,7]]}},"alternative-id":["2402"],"URL":"https:\/\/doi.org\/10.1007\/s11095-018-2402-9","relation":{},"ISSN":["0724-8741","1573-904X"],"issn-type":[{"type":"print","value":"0724-8741"},{"type":"electronic","value":"1573-904X"}],"subject":[],"published":{"date-parts":[[2018,4,27]]},"assertion":[{"value":"31 October 2017","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 April 2018","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 April 2018","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}],"article-number":"132"}}