Renal tolerance and pharmacokinetics of vancomycin in rats

Marre, R.; Schulz, E.; Anders, Thomas F.; Sack, K.

doi:10.1093/jac/14.3.253

Cited by 53 publications

(39 citation statements)

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“…Data obtained from animal studies may support this hypothesis (15,16). Marre et al demonstrated a significant reduction in vancomycin renal toxicity when rats received vancomycin in combination with D-glucaro-1,5-lactam, a substance known to protect against aminoglycoside-induced renal damage (16). Further studies in this area may allow us to correlate changes in AAP excretion with renal toxicity in this patient population.…”

Section: Discussionmentioning

confidence: 96%

“…In addition, the enhanced enzymuria that occurred in the vancomycin-gentamicin patients may indicate that the vancomycin mechanism of nephrotoxicity is similar to that of aminoglycosides. Data obtained from animal studies may support this hypothesis (15,16). Marre et al demonstrated a significant reduction in vancomycin renal toxicity when rats received vancomycin in combination with D-glucaro-1,5-lactam, a substance known to protect against aminoglycoside-induced renal damage (16).…”

Section: Discussionmentioning

confidence: 99%

“…Aminoglycosides have been well described as being nephrotoxic in both animals and humans, yet the potential of vancomycin for inducing renal damage remains controversial (2,6,11,(15)(16)(17)(18)(19)26). Wold and Turnipseed demonstrated that the combination of vancomycin and an aminoglycoside resulted in a higher incidence of nephrotoxicity in the rat model than either agent alone (28).…”

Section: Discussionmentioning

confidence: 99%

“…The plasma protein 02-microglobulin (P2M) and the proximal-tubule brush border enzyme alanine aminopeptidase (AAP) have been identified as sensitive indicators of renal injury (4, [18][19][20]26). While the mechanism of aminoglycoside-induced tubular toxicity has been described and shown to correlate with increased 12M and AAP urinary elimination, the vancomycin mechanism of action for nephrotoxicity has yet to be determined (1,16,17). In animal studies, kidney damage secondary to treatment with both aminoglycosides and vancomycin has been reported and the mechanisms of the drugs have been postulated as similar (1,15,16,28,29).…”

mentioning

confidence: 99%

“…While the mechanism of aminoglycoside-induced tubular toxicity has been described and shown to correlate with increased 12M and AAP urinary elimination, the vancomycin mechanism of action for nephrotoxicity has yet to be determined (1,16,17). In animal studies, kidney damage secondary to treatment with both aminoglycosides and vancomycin has been reported and the mechanisms of the drugs have been postulated as similar (1,15,16,28,29). To determine the significance of this potentiation of nephrotoxicity, we examined the elimination of AAP and P2M from patients receiving vancomycin alone, gentamicin alone, or concomitant vancomycin and gentamicin.…”

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confidence: 99%

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Alanine aminopeptidase and beta 2-microglobulin excretion in patients receiving vancomycin and gentamicin

Rybak

Frankowski

Edwards

et al. 1987

Antimicrob Agents Chemother

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The effects of vancomycin, gentamicin, and combination vancomycin-gentamicin treatments on alanine aminopeptidase (AAP) and 02-microglobulin (02M) elimination in 30 hospitalized patients were assessed and compared with elimination in a control group. Twenty-four-hour urine excretion values for AAP and j2M were determined on treatment day 1 and day 5 for patients receiving the three treatment regimens and for the control group. AAP excretion values for the vancomycin-treated group were not found to be statistically different from those of the control group. Both the gentamicin and the vancomycin-gentamicin groups had statistically higher AAP excretion values on treatment day 1 as well as on treatment day 5 when compared with the vancomycin and control groups. AAP excretion on day 5 of treatment was highest for the vancomycin-gentamicin group.Overall, ,2M elimination was variable in all treatment groups. Although the ,2M values were elevated as early as day 1 in all treatment groups, they were significantly elevated only in the vancomycin-gentamicin group on day 1 and only in the gentamicin group on day 5 compared with the vancomycin and the control groups. AAP appears to be a sensitive indicator of renal tubular damage. The combination of vancomycin and gentamicin results in greater AAP excretion than does either agent alone.

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Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Alanine aminopeptidase and beta 2-microglobulin excretion in patients receiving vancomycin and gentamicin

Rybak

Frankowski

Edwards

et al. 1987

Antimicrob Agents Chemother

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The Effect of Tobramycin on the Renal Handling of Vancomycin

Munar

Elzinga

Brummett

et al. 1991

The Journal of Clinical Pharma

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Studies in experimental animals and humans have suggested that enhanced renal and auditory toxicity occur with concurrent vancomycin and aminoglycoside treatment. In volunteers, systemic vancomycin clearance at steady-state was measured simultaneously with renal clearances of vancomycin, creatinine, inulin, and para-aminohippurate. Group 1 (n = 9) received vancomycin 5 mg/kg IV for 1 hour, then 1.1 mg/kg/hr for 3 hours. Group II (n = 7) received vancomycin plus tobramycin (2 mg/kg IV over 30 min). Groups did not differ demographically. Audiograms were obtained before and after vancomycin. Plasma samples were collected serially for vancomycin and tobramycin pharmacokinetic studies. Serum concentration versus time data were fit to a two-compartment model for vancomycin and a one-compartment model for tobramycin. For all volunteers, creatinine, inulin and para-aminohippurate clearance, and audiograms were not altered from baseline and were not statistically different between groups. No significant effect of tobramycin on vancomycin pharmacokinetics was observed. conversely, vancomycin had no significant effect on tobramycin pharmacokinetics. The nephrotoxic synergism of vancomycin and tobramycin is not explained by short-term differences in renal handling.

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In vivo evaluation of temperature‐responsive antimicrobial‐loaded PNIPAAm hydrogels for prevention of surgical site infection

et al. 2021

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Surgical site infections (SSIs) are a persistent clinical challenge. Local antimicrobial delivery may reduce the risk of SSI by increasing drug concentrations and distribution in vulnerable surgical sites compared to what is achieved using systemic antimicrobial prophylaxis alone. In this work, we describe a comprehensive in vivo evaluation of the safety and efficacy of poly(N-isopropylacrylamide-co-dimethylbutyrolactone acrylamideco-Jeffamine M-1000 acrylamide) [PNDJ], an injectable temperature-responsive hydrogel carrier for antimicrobial delivery in surgical sites. Biodistribution data indicate that PNDJ is primarily cleared via the liver and kidneys following drug delivery. Antimicrobial-loaded PNDJ was generally well-tolerated locally and systemically when applied in bone, muscle, articulating joints, and intraperitoneal space, although mild renal toxicity consistent with the released antimicrobials was identified at high doses in rats. Dosing of PNDJ at boneimplant interfaces did not affect normal tissue healing and function of orthopedic implants in a transcortical plug model in rabbits and in canine total hip arthroplasty.Finally, PNDJ was effective at preventing recurrence of implant-associated MSSA and MRSA osteomyelitis in rabbits, showing a trend toward outperforming commercially available antimicrobial-loaded bone cement and systemic antimicrobial administration.These studies indicate that antimicrobial-loaded PNDJ hydrogels are well-tolerated and could reduce incidence of SSI in a variety of surgical procedures.

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Renal tolerance and pharmacokinetics of vancomycin in rats

Cited by 53 publications

References 0 publications

Alanine aminopeptidase and beta 2-microglobulin excretion in patients receiving vancomycin and gentamicin

Alanine aminopeptidase and beta 2-microglobulin excretion in patients receiving vancomycin and gentamicin

The Effect of Tobramycin on the Renal Handling of Vancomycin

In vivo evaluation of temperature‐responsive antimicrobial‐loaded PNIPAAm hydrogels for prevention of surgical site infection

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