Vancomycin elimination

Park SS, Vallar RV, Hong CH, von Gun ten S, Ruoff K, D Amico DJ. Intravitreal dexamethasone effect on intra-vitreal vancomycin elimination in endophthalmitis. Arch Ophthalmol 1999 117(8) 1058-62. 

Now we are able to solve a vancomycin problem. A patient has a vancomycin elimination half life of 8h (elimination rate constant, 0.08663 h ) and a volume of distribution of 35 L. 

NaCNBH3 (10 mM) in phosphate buffer (pH = 3). The slurry is sonicated for 1 h, centrifuged, and the cyanoborohydride solution eliminated. The modified silica is washed with water and methanol, and then dried. This chemistry of binding provided for vancomycin a substantial bonding density of 120 p,mol/g (0.40 p,mol/m ) [70] (see Table 2.2). Surface coverage data for ristocetin A [75] and glycopeptide MDL 63,246 [43,44] were not provided by the authors. 

Drugs that may be affected by trospium include those eliminated by active tubular secretion (eg, digoxin, procainamide, pancuronium, morphine, vancomycin, metformin, and tenofovir). 

Metabolism/Excretion - In the first 24 hours, approximately 75% of a dose is excreted in urine by glomerular filtration. Elimination half-life is 4 to 6 hours in adults and 2 to 3 hours in children. About 60% of an intraperitoneal dose administered during peritoneal dialysis is absorbed systemically in 6 hours. Accumulation occurs in renal failure. Serum half-life in anephric patients is approximately 7.5 days. Vancomycin is not significantly removed by hemodialysis or continuous ambulatory peritoneal dialysis, although there have been reports of increased clearance with hemoperfusion and hemofiltration. 

Vancomycin is not absorbed after oral administration and must be given intravenously. Oral administrations are used for intraluminal gastrointestinal infections such as antibiotic-associated pseudomembranous colitis produced by Clostridium difficile. Vancomycin is widely distributed in the body but does not cross the blood brain barrier and does not penetrate into bone. It is excreted mainly via the urine, resulting in accumulation in patients with renal insufficiency. Its elimination half-life is 4-11 hours but can increase to 6-10 days in renal failure. 

Rifampin is used in a variety of other clinical situations. An oral dosage of 600 mg twice daily for 2 days can eliminate meningococcal carriage. Rifampin, 20 mg/kg/d for 4 days, is used as prophylaxis in contacts of children with Haemophilus influenzae type b disease. Rifampin combined with a second agent is used to eradicate staphylococcal carriage. Rifampin combination therapy is also indicated for treatment of serious staphylococcal infections such as osteomyelitis and prosthetic valve endocarditis. Rifampin has been recommended also for use in combination with ceftriaxone or vancomycin in treatment of meningitis caused by highly penicillin-resistant strains of pneumococci. 

Figure 17 Structure of the glycopeptide antibiotic vancomycin bound to the cell wall terminus D-Ala-D-Ala. Substitution of D-Ala-D-Ala for D-Ala-D-lactate eliminates an essential FI bond resulting in resistance.

Vancomycin is poorly absorbed from the gut and is given i.v. for systemic infections, as there is no satisfactory i.m. preparation. It distributes effectively into body tissues and is eliminated by the kidney. 

Vancomycin is eliminated almost exclusively by renal excretion. In oliguria 1 g can produce therapeutic plasma concentrations for 10-14 days. Hemodialysis fails to remove vancomycin from the body to any significant extent. If renal function is compromised, even oral therapy with vancomycin can lead to high and potentially toxic serum and CSF drug concentrations (109). 

Multiple-dose activated charcoal does not increase the elimination of vancomycin and is therefore not recommended for detoxification of acute poisoning (116). 

Intravitreal application of dexamethasone may reduce the elimination of intravitreal vancomycin and may enhance this therapy, as suggested by an in vivo study in rabbits (120). 

In patients with normal renal function, 70 to 90% of an intravenous dose of vancomycin is excreted in the urine unchanged by glomerular filtration. The serum elimination half-life in patients with normal renal function is variable, but averages 6 hours [171]. However, terminal half-lives ranging from 3 to 11 hours have been observed [184]. In anuric patients, the serum half-life increases markedly to 6 to 10 days [171]. The liver may also be involved in the disposition of vancomycin as dose adjustments have been required in patients with severe liver dysfunction [172]. An interesting study by Golper et al that compared systemic vancomycin clearance simultaneously with the renal clearances of vancomycin, creatinine, inulin and para-aminohippurate demonstrated a substantial non-renal clearance of vancomycin of 30%. In addition, the researchers found that the non-renal clearance of vancomycin was concentration dependent with a 10% greater clearance at serum concentrations of 14 mg/ ml as compared to 7 mg/ ml [185]. 

Presentation 1 Conclusion Both vancomycin and tobramycin are adnriinistered with dosing intervals that are longer than the drugs T54. Under these conditions there is little accumulation, and loading doses are not usually administered. Both vancomycin and tobramycin are eliminated from the body primarily by the renal route. BK is a 72-year-old man with a serum Cr level of 2.4 mgAjL As a first estimate, his renal function would appear to be approximately half of the normal value. Using the equation that accounts for age, body size, sex, and serum Cr, his estimated CrCI rate is expected to be approximately 25 ml/min. 

Figure 8 Stepwise elimination of noninteracting peptides from a mixture of 32 peptides and identification of one tight-binding ligand for vancomycin. Interpretation of each electropherogram is described in the text. Specific experimental conditions are described elsewhere (86a). (Reproduced with permission of the copyright holder, publisher and Journal of Organic Chemistry.)...

Vancomycin requires multicompartment models to completely describe its serum-concentration-versus-time curves. However, if peak serum concentrations are obtained after the distribution phase is completed (usually V2 to 1 hour after a 1-hour intravenous infusion), a one-compartment model can be used for patient dosage calculations. Also, since vancomycin has a relatively long half-life compared with the infusion time, only a small amount of drug is eliminated during infusion, and it is usually not necessary to use more complex intravenous infusion equations. Thus simple intravenous bolus equations can be used to calculate vancomycin doses for most patients. Although a recent review paper questioned the clinical usefulness of measuring vancomycin concentrations on a routine basis, research articles" " have shown potential benefits in obtaining vancomycin concentrations... 

Renal elimination Elimination of gentamicin, vancomycin, cephalosporins less than predicted by serum creatinine ... 

Peak and/or trough concentrations are monitored rontinely for only a select few antimicrobials (e.g., aminoglycosides and vancomycin) during the contemporary management of infections. It is crucial for the health care team to ensure that the antimicrobiars administration time and serum sample time(s) are meticulously recorded because even small errors in recording these (e.g., 1 hour) may have a substantial impact on the calcnlation of pharmacokinetics for antibiotics such as the aminoglycosides, which have relatively short elimination half-lives. 

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