Quantitative estimation of renal clearance of N-acetylprocainamide in rats with various experimental acute renal failure.
The dosage regimen of a drug eliminated predominantly through the kidney need to be adjusted for the patients with renal disease. The objective of the present study was to establish a quantitative approach to precisely predicting the renal clearances of basic drugs using N-1-methylnicotinamide (NMN). A variety of experimental acute renal failure (ARF) in rats were prepared and N-acetylprocainamide (NAPA) was used as a model drug. The renal clearances of NAPA were significantly decreased in rats with ARF, resulting in significantly increased plasma concentrations. Remarkable reduction in clearance ratios (CL(ratio)) was observed, indicating that the impairment in tubular and glomerular function did not proceed in a parallel manner. The renal clearance of NAPA (CL(rNAPA)) was better predicted from the renal clearance of NMN (CL(rNMN)) than from GFR. A mathematical equation was also constructed to estimate the CL(rNMN) from the NMN plasma concentration. Therefore, the renal clearance of basic drugs excreted predominantly from the kidney can be easily and more accurately estimated based on the concentrations of endogenous NMN to provide a precise dosage regimen for patients with renal failure.
He
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YL
Department of Anaesthesia and Critical Care, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, Boston, MA 02114, USA. Yhe@partners.org
Kitada
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N
Yasuhara
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Hori
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R
D000120:Acecainide / Q000493:pharmacokinetics* / Q000652:urine*; D058186:Acute Kidney Injury / Q000652:urine*; D000818:Animals; D001798:Blood Proteins / Q000378:metabolism; D005919:Glomerular Filtration Rate; D006029:Glycosuria / Q000652:urine; D007677:Kidney Function Tests; D008297:Male; D011485:Protein Binding; D011507:Proteinuria / Q000652:urine; D051381:Rats; D017208:Rats, Wistar; D012079:Renal Circulation
D001798:Blood Proteins; D000120:Acecainide