Vancomycin distribution

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. 

Teicoplanin, like vancomycin, is not absorbed from the intestinal tract. Peak plasma levels are achieved about 2 hours after intramuscular administration. The drug distributes widely in tissues plasma protein binding is about 90%. The half-Ufe approximates 50 hours, which is considerably longer than that of vancomycin, and may make it useful for outpatient administration. Like vancomycin, teicoplanin is excreted by the kidneys. 

Vancomycin is poorly absorbed from the intestinal tract and is administered orally only for the treatment of antibiotic-associated enterocolitis caused by C difficile. Parenteral doses must be administered intravenously. A 1-hour intravenous infusion of 1 g produces blood levels of 15-30 mcg/mL for 1-2 hours. The drug is widely distributed in the body. Cerebrospinal fluid levels 7-30% of simultaneous serum concentrations are achieved if there is meningeal... 

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. 

Ngeleka M, Auclair P, Tardif D, Beauchamp D, Bergeron MG. Intrarenal distribution of vancomycin in endotoxemic rats. Antimicrob Agents Chemother 1989 33(9) 1575-9. 

Data and clinical experience with hemofiltration and hemodiafiltration for blood purification are limited. This modality has been used to remove large molecule antibiotics such as aminoglycosides and vancomycin [30]. Extended treatments may be of benefit in the removal of drugs with tight tissue binding, large volumes of distribution, and slow equilibration with the plasma such as procainamide [31]. However, there is a report of the failure of continuous hemofiltration to clear the antiarrhythmic drug flecainide [32]. 

Vancomycin is approximately 30 to 55% bound to plasma proteins. Its distribution after intravenous administration proceeds as a biphasic process and is consistent with a two or three compartment model. The half-life of the first distributive phase is approximately 0.4 hour in patients with normal renal function the second distributive phase is approximately 1.6 hours [172]. Consistent with its multicompartment pharmacokinetic modeling, vancomycin is widely distributed and penetrates into many different body fluids and... 

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... 

Initial doses of vancomycin can be computed for adult patients using estimated kinetic parameters derived from population pharmacokinetic data. Clearance is estimated using the patient s creatinine clearance in the following equation" Cl (in mL/min/kg) = 0.695(CrCl in mL/min/kg) -L 0.05. The volume of distribution is computed assuming the standard value of 0.7 L/kg = 0.7(Wt),... 

Monitoring vancomycin serum concentrations is not cost-effective in preventing vancomydn-induced nephrotoxicity in patients with normal renal function, since the correlation between serum levels and antibacterial efficacy or toxicity remains controversial [185, 186, 182]. Serum level determination may be helpful in patients with increased volume of distribution, in patients with decreased renal function, in children or neonates, and in the elderly [165]. 

ABSORPTION, DISTRIBUTION, AND EXCRETION Vancomycin is poorly absorbed after oral administration. For parenteral therapy, the drug should be administered intravenously. The drug has a serum elimination t, of 6 hours. Approximately 30% of vancomycin is bound to plasma protein. Vancomycin appears in various body fluids, including the CSF when the meninges are inflamed, bile, and pleural, pericardial, synovial, and ascitic fluids. About 90% of an injected dose is excreted by glomerular filtration. 

The importance of the serial route in transmission of antibiotic-resistant staphylococci can be indirectly illustrated by findings in the environment, patients and the nursing personnel of a surgical clinic in Bratislava (Czechoslovakia) [8j. The results were obtained during corroborative studies on the distribution of resistant staphylococci from different environments in Slovakia [11]. The strains of coagulase-positive strains of Staphylococcus aureus from the clinic were tested for their sensitivity to six common antibiotics of that time. With staphylococci isolated from the environment, patients and the personnel, the percentages of resistance to benzylpeni-cillin, streptomycin, chlorotetracycline, erythromycin, chloramphenicol and vancomycin are shown in Fig. 6.1. The percentages of resistance to the individual antibiotics were positively correlated with the consumption of their preparations at the clinic. 

Teicoplanin is a mixture of five related fermentation products related to vancomycin. It is more lipid soluble and, therefore, distributes better into tissues and bacteria. It also is highly protein bound, so it can be used IM or IV once daily. It is markedly less irritating than vancomycin on injection therefore, it appears to be better tolerated by patients and on IV administration. It is not presently available in the United States but is available in a number of other countries. The glycopeptide field is under intense investigation, and a number of agents are at various stages of preclinical evaluation. 

Historically, vancomycin serum concentrations have been monitored and adjusted using first-order pharmacokinetic calculations (see aminoglycosides). However, difficulty obtaining a reliable peak concentration because of the initial distribution phase and lack of correlation between serum concentrations and efficacy and toxicity have led to a reappraisal of the value of pharmacokinetic monitoring with vancomycin. 

The aminoglycoside antibiotics display some two-compartment characteristics, but not as markedly as vancomycin. For a 1 h infusion, the tme peak plasma gentamicin concentration (immediately after the infusion is stopped) is often used. The rationale for this is that distribution equilibrium for gentamicin is essentially complete in 1 h. However, for a 30 min infusion, it is common to wait for an additional 30 min after the infusion is stopped and to call this the gentamicin "peak" concentration. 

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. 

Goldstein F, Coutrot A, Seiffet A, Acar JF. Percentages distributions of teicoplanin- and vancomycin-resistant strains among coagulase-negative staphylococci. Antimicrob Agents Chemother 1990 34 899-900. 

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