Renal Interaction Between Itraconazole and Cimetidine
dc.contributor.author | Karyekar, Chetan S. | |
dc.contributor.author | Eddington, Natalie D. | |
dc.contributor.author | Briglia, Andrew | |
dc.contributor.author | Gubbins, Paul O. | |
dc.contributor.author | Dowling, Thomas C. | |
dc.date.accessioned | 2011-12-05T15:18:40Z | |
dc.date.available | 2011-12-05T15:18:40Z | |
dc.date.issued | 2004 | |
dc.identifier.citation | Karyekar, 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.issn | 0091-2700 | |
dc.identifier.issn | 1552-4604 | |
dc.identifier.uri | http://hdl.handle.net/10713/702 | |
dc.description.abstract | Renal 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 warranted | en_US |
dc.description.uri | http://dx.doi.org/10.1177/0091270004266783 | en_US |
dc.language.iso | en_US | en_US |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/4.0/ | |
dc.subject | renal tubular secretion | en_US |
dc.subject | renal drug interactions | en_US |
dc.subject.mesh | Cimetidine | en_US |
dc.subject.mesh | Drug Interactions | en_US |
dc.subject.mesh | Itraconazole | en_US |
dc.subject.mesh | Kidney | en_US |
dc.title | Renal Interaction Between Itraconazole and Cimetidine | en_US |
dc.type | Article | en_US |
refterms.dateFOA | 2019-02-20T19:58:05Z |