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• W2063671394 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 (CL sec ) of cimetidine was calculated as the difference between renal clearance (CL r ) and GFR (CL ioth ) on days 1 and 5. Cimetidine pharmacokinetic estimates were obtained for total clearance (CL T ), volume of distribution (Vd), elimination rate constant (K el ), area under the plasma concentration‐time curve (AUC 0–240 min ), and average plasma concentration (Cp ave ) before and after itraconazole administration. Plasma itraconazole concentrations following oral dosing ranged from 0.41 to 0.92 μg/mL. The cimetidine AUC 0–240 min increased by 25% (p < 0.01) following itraconazole administration. The GFR and Vd remained unchanged, but significant reductions in CL T (655 vs. 486 mL/min, p < 0.001) and CL sec (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‐gp‐mediated renal tubular secretion. Further evaluation of renal P‐gp‐modulating drugs such as itraconazole that may alter the renal excretion of coadministered drugs is warranted." @default.
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• W2063671394 date "2004-08-01" @default.
• W2063671394 modified "2023-10-13" @default.
• W2063671394 title "Renal Interaction Between Itraconazole and Cimetidine" @default.
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• W2063671394 doi "https://doi.org/10.1177/0091270004266783" @default.
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