IngentaConnect Effect Of Organic Cations On The Renal Tubular Secretion Of Pseud...

Authors: Strindelius, Lena C; Nation, Roger L; Evans, Allan M; Cabot, Juanita L; Corbett, Kathryn M

Source: Clinical and Experimental Pharmacology and Physiology, Volume 28, Numbers 1-2, January/February 2001 , pp. 43-47(5)

Publisher: Blackwell Publishing

Abstract:

SUMMARY

1. Pseudoephedrine is a weak organic base that undergoes renal tubular secretion. The aim of the present study was to assess whether two other commonly used weak organic bases (cimetidine and morphine) inhibit the renal tubular secretion of pseudoephedrine in the rat isolated perfused kidney.

2. A total of 12 perfusions were performed with four perfusions in each of three treatment groups. In the control group, pseudoephedrine was administered as a bolus dose of [¹⁴C]-pseudoephedrine and unlabelled pseudoephedrine to achieve an initial perfusate concentration of 0.4 μg/mL. For the treatment groups, pseudoephedrine was administered as above and cimetidine or morphine was added to the perfusion medium in increasing concentrations of 0.5-12.5 and 0.2-5.0 μg/mL, respectively.

3. The mean (±SD) fraction unbound of pseudoephedrine alone in perfusate was 0.866±0.014 and was not different (P > 0.05) in the presence of cimetidine or morphine.

4. In control experiments, the renal excretory clearance (CL_R) of pseudoephedrine was three-fold greater than glomerular filtration rate (GFR), yielding a ratio consistently greater than unity, which indicates extensive net tubular secretion of pseudoephedrine. The CL_R and total clearance of pseudoephedrine were similar, suggesting an absence of renal metabolism of pseudoephedrine.

5. The CL_R/GFR ratio for pseudoephedrine was not affected by morphine, but was significantly reduced (P < 0.05) in the presence of cimetidine.

6. The results indicate that cimetidine inhibits the renal tubular secretion of pseudoephedrine.

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Effect Of Organic Cations On The Renal Tubular Secretion Of Pseudoephedrine In The Rat