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The Urinary Excretion of Metformin, Ceftizoxime and Ofloxacin in High Serum Creatinine Rats: Can Creatinine Predict Renal Tubular Elimination?

The Urinary Excretion of Metformin, Ceftizoxime and Ofloxacin in High Serum Creatinine Rats: Can Creatinine Predict Renal Tubular Elimination?

Yan-Rong Ma, Yan Zhou, Jing Huang, Hong-Yan Qin, Pei Wang, Xin-An Wu

Life Sci. 2018 Mar 1;196:110-117.

PMID: 29355545

Abstract:

The renal excretion of creatinine and most drugs are the net result of glomerular filtration and tubular secretion, and their tubular secretions are mediated by individual transporters. Thus, we hypothesized that the increase of serum creatinine (SCr) levels attributing to inhibiting tubular transporters but not glomerular filtration rate (GFR) could be used to evaluate the tubular excretion of drugs mediated by identical or partial overlap transporter with creatinine. In this work, we firstly developed the creatinine excretion inhibition model with normal GFR by competitively inhibiting tubular transporters, and investigated the renal excretion of metformin, ceftizoxime and ofloxacin in vivo and in vitro. The results showed that the 24-hour urinary excretion of metformin and ceftizoxime in model rats were decreased by 25% and 17% compared to that in control rats, respectively. The uptake amount and urinary excretion of metformin and ceftizoxime could be inhibited by creatinine in renal cortical slices and isolated kidney perfusion. However, the urinary excretion of ofloxacin was not affected by high SCr. These results showed that the inhibition of tubular creatinine transporters by high SCr resulted to the decrease of urinary excretion of metformin and ceftizoxime, but not ofloxacin, which implied that the increase of SCr could also be used to evaluate the tubular excretion of drugs mediated by identical or partial overlap transporter with creatinine in normal GFR rats.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP68401810	Ceftizoxime		68401-81-0	Price

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