{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T20:47:19Z","timestamp":1760042839764},"reference-count":37,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2013,3,8]],"date-time":"2013-03-08T00:00:00Z","timestamp":1362700800000},"content-version":"vor","delay-in-days":3141,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2004,8]]},"abstract":"<jats:p>Renal drug interactions can result from competitive inhibition between drugs that undergo extensive renal tubular secretion by transporters such as P\u2010glycoprotein (P\u2010gp). The purpose of this study was to evaluate the effect of itraconazole, a known P\u2010gp inhibitor, on the renal tubular secretion of cimetidine in healthy volunteers who received intravenous cimetidine alone and following 3 days of oral itraconazole (400 mg\/day) administration. Glomerular filtration rate (GFR) was measured continuously during each study visit using iothalamate clearance. Iothalamate, cimetidine, and itraconazole concentrations in plasma and urine were determined using high\u2010performance liquid chromatography\/ultraviolet (HPLC\/UV) methods. Renal tubular secretion (CL<jats:sub><jats:italic>sec<\/jats:italic><\/jats:sub>) of cimetidine was calculated as the difference between renal clearance (CL<jats:sub><jats:italic>r<\/jats:italic><\/jats:sub>) and GFR (CL<jats:sub><jats:italic>ioth<\/jats:italic><\/jats:sub>) on days 1 and 5. Cimetidine pharmacokinetic estimates were obtained for total clearance (CL<jats:sub><jats:italic>T<\/jats:italic><\/jats:sub>), volume of distribution (Vd), elimination rate constant (K<jats:sub><jats:italic>el<\/jats:italic><\/jats:sub>), area under the plasma concentration\u2010time curve (AUC<jats:sub><jats:italic>0\u2013240 min<\/jats:italic><\/jats:sub>), and average plasma concentration (Cp<jats:sub><jats:italic>ave<\/jats:italic><\/jats:sub>) before and after itraconazole administration. Plasma itraconazole concentrations following oral dosing ranged from 0.41 to 0.92 \u03bcg\/mL. The cimetidine AUC<jats:sub><jats:italic>0\u2013240 min<\/jats:italic><\/jats:sub> increased by 25% (p &lt; 0.01) following itraconazole administration. The GFR and Vd remained unchanged, but significant reductions in CL<jats:sub><jats:italic>T<\/jats:italic><\/jats:sub> (655 vs. 486 mL\/min, <jats:italic>p<\/jats:italic> &lt; 0.001) and CL<jats:sub><jats:italic>sec<\/jats:italic><\/jats:sub> (410 vs. 311 mL\/min, <jats:italic>p<\/jats:italic> = 0.001) were observed. The increased systemic exposure of cimetidine during coadministration with itraconazole was likely due to inhibition of P\u2010gp\u2010mediated renal tubular secretion. Further evaluation of renal P\u2010gp\u2010modulating drugs such as itraconazole that may alter the renal excretion of coadministered drugs is warranted.<\/jats:p>","DOI":"10.1177\/0091270004266783","type":"journal-article","created":{"date-parts":[[2004,7,15]],"date-time":"2004-07-15T01:32:39Z","timestamp":1089855159000},"page":"919-927","source":"Crossref","is-referenced-by-count":26,"title":["Renal Interaction Between Itraconazole and Cimetidine"],"prefix":"10.1002","volume":"44","author":[{"given":"Chetan S.","family":"Karyekar","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natalie D.","family":"Eddington","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew","family":"Briglia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul O.","family":"Gubbins","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas C.","family":"Dowling","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2013,3,8]]},"reference":[{"key":"e_1_2_5_2_2","doi-asserted-by":"publisher","DOI":"10.1177\/00912709922012006"},{"key":"e_1_2_5_3_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1025733918160"},{"key":"e_1_2_5_4_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.2001.00461.x"},{"key":"e_1_2_5_5_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.84.21.7735"},{"key":"e_1_2_5_6_2","doi-asserted-by":"publisher","DOI":"10.1159\/000190289"},{"key":"e_1_2_5_7_2","first-page":"A686","article-title":"Characteristics of itraconazole and ketoconazole inhibition of digoxin transport across renal tubular cells","volume":"9","author":"Ito S","year":"1995","journal-title":"FASEB J"},{"key":"e_1_2_5_8_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.1999.277.1.F84"},{"key":"e_1_2_5_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/0005-2736(90)90074-X"},{"key":"e_1_2_5_10_2","first-page":"525","article-title":"Handling of doxorubicin by the LLCPK1 kidney cell line","volume":"286","author":"Decorti G","year":"1998","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_2_5_11_2","doi-asserted-by":"publisher","DOI":"10.1002\/jps.2600690408"},{"key":"e_1_2_5_12_2","first-page":"271","article-title":"Comparison of famotidine with cimetidine and ranitidine","volume":"7","author":"Berardi RR","year":"1988","journal-title":"Clin Pharm"},{"key":"e_1_2_5_13_2","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-198308060-00001"},{"key":"e_1_2_5_14_2","first-page":"1","article-title":"Enhanced transepithelial flux of cimetidine by Madin\u2010Darby canine kidney cells overexpressing human P\u2010glycoprotein","volume":"270","author":"Pan BF","year":"1994","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_2_5_15_2","first-page":"1254","article-title":"P\u2010glycoprotein and organic cation secretion by the mammalian kidney","volume":"269","author":"Dutt A","year":"1994","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_2_5_16_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1011089924099"},{"key":"e_1_2_5_17_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00663011"},{"key":"e_1_2_5_18_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI115154"},{"key":"e_1_2_5_19_2","doi-asserted-by":"publisher","DOI":"10.1097\/00007691-199712000-00001"},{"key":"e_1_2_5_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0009-9236(97)90046-1"},{"key":"e_1_2_5_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-4347(98)00294-1"},{"key":"e_1_2_5_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchromb.2003.10.030"},{"key":"e_1_2_5_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0731-7085(97)00062-9"},{"key":"e_1_2_5_24_2","first-page":"S11","article-title":"P\u2010glycoprotein functions and substrates: possible roles of MDR1 gene in the kidney","volume":"65","author":"Ernest S","year":"1998","journal-title":"Kidney Int Suppl"},{"key":"e_1_2_5_25_2","doi-asserted-by":"publisher","DOI":"10.1592\/phco.23.4.436.32125"},{"key":"e_1_2_5_26_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1996.tb15612.x"},{"key":"e_1_2_5_27_2","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(19940801)74:3<834::AID-CNCR2820740308>3.0.CO;2-9"},{"key":"e_1_2_5_28_2","first-page":"1741","article-title":"Reversal of multidrug resistance by PSC833, combined with VAD (vincristine, doxorubicin, dexamethasone) in refractory multiple myeloma: a phase I study","volume":"10","author":"Sonneveld P","year":"1996","journal-title":"Leukemia"},{"key":"e_1_2_5_29_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1681.1996.tb01155.x"},{"key":"e_1_2_5_30_2","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-198916010-00003"},{"key":"e_1_2_5_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)63784-6"},{"key":"e_1_2_5_32_2","first-page":"866","article-title":"OATP and P\u2010glycoprotein transporters mediate the cellular uptake and excretion of fexofenadine","volume":"27","author":"Cvetkovic M","year":"1999","journal-title":"Drug Metab Dispos"},{"key":"e_1_2_5_33_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1018825819249"},{"key":"e_1_2_5_34_2","doi-asserted-by":"publisher","DOI":"10.1001\/archotol.1993.01880190049010"},{"key":"e_1_2_5_35_2","doi-asserted-by":"publisher","DOI":"10.2174\/1389200003339135"},{"key":"e_1_2_5_36_2","doi-asserted-by":"publisher","DOI":"10.1067\/mcp.2000.110772"},{"key":"e_1_2_5_37_2","doi-asserted-by":"publisher","DOI":"10.1007\/s002130050715"},{"key":"e_1_2_5_38_2","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1016\/0016-5085(80)90685-X","article-title":"Dose and serum concentration relationships in cimetidine\u2010associated mental confusion","volume":"78","author":"Kimelblatt BJ","year":"1980","journal-title":"Gastroenterology"}],"container-title":["The Journal of Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1177%2F0091270004266783","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/pdf\/10.1177\/0091270004266783","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,12]],"date-time":"2023-10-12T11:11:10Z","timestamp":1697109070000},"score":1,"resource":{"primary":{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/10.1177\/0091270004266783"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2004,8]]},"references-count":37,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2004,8]]}},"alternative-id":["10.1177\/0091270004266783"],"URL":"https:\/\/doi.org\/10.1177\/0091270004266783","archive":["Portico"],"relation":{},"ISSN":["0091-2700","1552-4604"],"issn-type":[{"value":"0091-2700","type":"print"},{"value":"1552-4604","type":"electronic"}],"subject":[],"published":{"date-parts":[[2004,8]]}}}