Renal Excretion of Vancomycin in Rats with Acute Renal Failure

Abstract

We have investigated the renal excretion of vancomycin in rats with acute renal failure (ARF) induced by uranyl nitrate or cisplatin. The renal clearance of the antibiotic after uranyl nitrate or cisplatin injection was separately evaluated by calculating the glomerular filtration rate (GFR) and secretory clearance. The reduced renal clearance of vancomycin in these ARF rats was a result of a decrease in both GFR and secretory clearance. The extents of the decreases in GFR and in secretory clearance were not, however, proportional, the extent of the decrease in secretory clearance being more pronounced. These results suggest that the renal tubular secretion of vancomycin was reduced more predominantly than glomerular filtration in these ARF models.

Effects of Fosfomycin and Imipenem-Cilastatin on the Nephrotoxicity of Vancomycin and Cisplatin in Rats

“…The pharmacokinetic parameters of vancomycin were calculated on the basis of standard procedures for each experimental period in clearance studies (Nakamura et al 1997). Renal clearance was determined as the urinary excretion rate divided by the steady-state plasma concentration.…”

“…The renal clearance of vancomycin was estimated in rats with acute renal failure induced by vancomycin 2 days after vancomycin injection. The invivo clearance study was performed as described previously (Nakamura et al 1997). Brie¯y, control rats and rats with acute renal failure were anaes-thetized by intraperitoneal administration of 50 or 30 mg kg 71 pentobarbital, respectively.…”

“…We have previously used an in-vivo clearance study to examine the renal excretion of vancomycin in normal rats and rats with acute renal failure; we showed that the antibiotic is secreted via the renal tubules. In addition, tubular secretion of vancomycin is reduced more markedly than its glomerular ®ltration in rats with acute renal failure induced by uranyl nitrate and cisplatin (Nakamura et al 1996(Nakamura et al , 1997. It has been reported that some antibiotics might reduce the nephrotoxicity of vancomycin (Toyoguchi & Nakagawa 1996).…”

Pharmacokinetics of etoposide in rats with uranyl nitrate (UN)-induced acute renal failure (ARF): Optimization of the duration of UN dosing

“…A number of studies have been published confirming the pharmacokinetic alterations in UN-ARF rats (4)(5)(6)(7)(8)1112,(16)(17)(18)(19). Due to the various study protocols adopted for the investigation of the pharmacokinetics/pharmacodynamics of the compound in UN-ARF rats, it appeared to be important to establish a specific protocol.…”

“…Uranyl nitrate-induced acute renal failure (UN-ARF) has been shown to affect hepatic cytochrome P450 activity by inducing the expression of certain cytochrome P450 (CYP) isozymes such as CYP 2E 1 and 3A23, while inhibiting the expression of others such as CYP 2C 11. Hence, both renal and non-renal clearance (CL) is subject to alteration in the case of UN-ARF, as shown by pharrnacokinetic data regarding a large number of drugs such as renally eliminated vancomycin, methotrexate and hepatic ally eliminated theophylline, amiodarone and diltiazem (4)(5)(6)(7)(8). Due to the above, renal failure has been shown to increase the bioavailability of certain drugs.…”