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dc.contributor.authorKaryekar, Chetan S.
dc.contributor.authorEddington, Natalie D.
dc.contributor.authorBriglia, Andrew
dc.contributor.authorGubbins, Paul O.
dc.contributor.authorDowling, Thomas C.
dc.date.accessioned2011-12-05T15:18:40Z
dc.date.available2011-12-05T15:18:40Z
dc.date.issued2004
dc.identifier.citationKaryekar, C. S., Eddington, N. D., Briglia, A., Gubbins, P. O., & Dowling, T. C. (2004). Renal interaction between itraconazole and cimetidine. Journal of Clinical Pharmacology, 44(8), 919-927, DOI: 10.1177/0091270004266783.en_US
dc.identifier.issn0091-2700
dc.identifier.issn1552-4604
dc.identifier.urihttp://hdl.handle.net/10713/702
dc.description.abstractRenal drug interactions can result from competitive inhibition between drugs that undergo extensive renal tubular secretion by transporters such as P-glycoprotein (P-gp). The purpose of this study was to evaluate the effect of itraconazole, a known P-gp 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-performance liquid chromatography/ ultraviolet (HPLC/UV) methods. Renal tubular secretion (CLsec) of cimetidine was calculated as the difference between renal clearance (CLr) andGFR (CLioth) ondays 1 and 5. Cimetidine pharmacokinetic estimates were obtained for total clearance (CLT), volume of distribution (Vd), elimination rate constant (Kel), area under the plasma concentrationtime curve (AUC0-240 min), and average plasma concentration (Cpave) before and after itraconazole administration. Plasma itraconazole concentrations following oral dosing ranged from 0.41 to 0.92 μg/mL. The cimetidine AUC0-240 min increased by 25% (p < 0.01) following itraconazole administration. The GFR and Vd remained unchanged, but significant reductions in CLT (655 vs. 486 mL/min, p < 0.001) and CLsec (410 vs. 311 mL/min, p = 0.001) were observed. The increased systemic exposure of cimetidine during coadministration with itraconazole was likely due to inhibition of P-gpmediated renal tubular secretion. Further evaluation of renal P-gp-modulating drugs such as itraconazole thatmay alter the renal excretion of coadministered drugs is warranteden_US
dc.description.urihttp://dx.doi.org/10.1177/0091270004266783en_US
dc.language.isoen_USen_US
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectrenal tubular secretionen_US
dc.subjectrenal drug interactionsen_US
dc.subject.meshCimetidineen_US
dc.subject.meshDrug Interactionsen_US
dc.subject.meshItraconazoleen_US
dc.subject.meshKidneyen_US
dc.titleRenal Interaction Between Itraconazole and Cimetidineen_US
dc.typeArticleen_US
refterms.dateFOA2019-02-20T19:58:05Z


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