Vancomycin pharmacokinetics

Macias WL, Mueller BA, Scarim KS. Vancomycin pharmacokinetics in acute renal failure Preservation of nonrenal clearance. Clin Pharmacol Ther 1991 50 688-94. 

GolperTA, Noonan HM, Elzinga L,Gilbert D, Brummett R, Anderson JL, Bennett WM,Vancomycin pharmacokinetics, renal handling and nonrenal clearances in normal human subjects, Clin Pharmacol Ther, 1988,43(5) 565-70. 

Rodvold KA, Blum RA, Fischer JH, Zokufa HZ, Rotschafer JC, Crossley KB, Riff LJ, Vancomycin pharmacokinetics in patient with various degrees of renal function, Antimicrob Agent Chemother, 1988,32(6) 848-52. 

Blouin RA, Bauer LA, Miller DD, el al. Vancomycin pharmacokinetics in normal and morbidly obese subjects. Antimicrob Agents Chemother 1982 21 575-580. 

Magera BE, Arroyo JC, Rosansky SJ, Postic B. Vancomycin pharmacokinetics in patients with peritonitis on peritoneal dialysis. Antimicrob Agents Chemother 1983 23 710-714. 

Hagan NB, MacDonald JL, Liang K-C, Womack SJ. Vancomycin pharmacokinetics in low biitii weight preterm neonates on therapeutic doses of theopl lline. Pediatr Res (1996) 39, 74A. 

Obtain serum drug levels for aminoglycosides and/or vancomycin and perform pharmacokinetic analysis. Adjust the dose, if needed, according to the parameters in Table 13-2. Obtain follow-up trough levels at weekly intervals or sooner if renal function is unstable. Follow serum creatinine levels if renal function is unstable. Hearing tests may be scheduled yearly or per patient preference. 

Pharmacology Vancomycin is a tricyclic glycopeptide antibiotic that inhibits cell-wall biosynthesis. It also alters bacterial-cell-membrane permeability and RNA synthesis. Pharmacokinetics ... 

This family is exemplified by moenomycin A 77, a major representative of moeno-mycin complex produced by S. ghanaensis (ATCC14672). Compound 77 is one of the most potent antibiotics known to date it is active against many vancomycin-and methicillin-resistant pathogens [141]. Moenomycin A suffers from poor pharmacokinetics, prompting the search for improved analogs that are suitable for treating human diseases. 

Pharmacokinetics Slow intravenous infusion is employed for treatment of systemic infections or for prophylaxis. Because vancomycin is not absorbed after oral administration, this route is only employed for the treatment of antibiotic-induced colitis due to Q difficile. Inflammation allows penetration into the meninges. Metabolism is minimal 90-100 % is excreted by glomerular filtration. [Note Dosage must be adjusted in renal failure since the drug will accumulate. Normal half-life is 6-10 hours compared to over 200 hours in end-stage renal disease.]... 

Davies SP, Azadian BS, Kox WJ, Brown EA. Pharmacokinetics of ciprofloxacin and vancomycin in patients with acute renal failure treated by continuous haemodialysis. Nephrol Dial Transplant 1992 7 848-54. 

Rogge, M.C. Johnson, C.A. Zimmermann, S.W. Welling, P.G. Vancomycin disposition during continuous ambulatory peritoneal dialysis a pharmacokinetic analysis of peritoneal drug transport. Antimcrob. Ag. Chemother. 1985, 27, 578-582. 

Harding 1, Sorgel F. Comparative pharmacokinetics of teicoplanin and vancomycin. J Chemother 2000 12(Suppl 5) 15-20. 

Changes in pharmacokinetics were studied in male Wistar rats when intravenous vancomycin 100 mg/kg and levofloxacin 20 mg/kg were administered together (124). There was an increase in the AUC and half-hfe of vancomycin. There was also an increase in the AUC and a delay in the t ax of levofloxacin, but no effect on Cmaxi these data suggested delayed absorption of levofloxacin. Concomitant administration had no effect on the correlation between serum and hepatic tissue concentrations of levofloxacin, but it markedly reduced the correlation between the serum and renal tissue concentrations of vancomycin. Vancomycin increased serum creatinine concentrations 8 hours after administration. However, there was no difference in animals who received monotherapy compared with animals who received combined therapy. The authors suggested the cautious use of a combination of levofloxacin and vancomycin and advised monitoring blood concentrations of vancomycin in such cases. 

Pharmacokinetics of vancomycin Renal transport of vancomycin Epidemiology of vancomycin nephrotoxicity Risk factors for nephrotoxicity Therapeutic drug monitoring of vancomycin Prevention of vancomycin nephrotoxicity Alternative gram positive antibiotics References ... 

Vancomycin exhibits predictable pharmacokinetic properties and its clinical use has been guided by the pharmacokinetic monitoring of serum levels to determine the dose and frequency of administration. Pharmacokinetic monitoring of vancomycin, however, has become increasingly controversial given the improved safety of this antibiotic and the lack of data to support what are considered the therapeutic and toxic serum levels. Historically, the most severe toxicities of vancomycin were ototoxicity and nephrotoxicity. The incidence of nephrotoxicity has declined since its introduction possibly due to the availability of purer forms of the antibiotic. Ototoxicity has always been a rare adverse event of vancomycin, but it has been observed with excessively high concentrations of the drug in plasma [170-172]. The purpose of this section is to describe the nephrotoxicity associated with the clinical use of vancomycin. 

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... 

Darko W, Medicis JJ, Smith A, Guharoy R, Lehmann DF, Mississippi mud no more cost-effectiveness of pharmacokinetic dosage adjustment of vancomycin to prevent nephrotoxicity, Pharmacother, 2003,23(5) 643-50 197. 

Oritavancin is a semi-synthetic derivative of vancomycin, and differs from the parent compound by the presence of an additional 4-ej3z-vancosamine and a p-chlorodiphenyl side chain to the additional vancosamine. These modifications confer unusual pharmacodynamic and pharmacokinetic properties on oritavancin. Oritavancin exhibits rapid and concentration-dependent bactericidal activity against gram-positive bacteria in association with a prolonged postantibiotic efifeci... 

Antibiotics that require TDM include aminoglycosides, chloramphenicol, sulfonamides, vancomycin, trimethoprim, P-lactams, and tetracyclines. Pharmacokinetic details of these antibiotics are summarized in Table 33-4. Aminoglycosides and vancomycin are quantified by immmioassay. Other antibiotics have been measured by HPLC. 

In 1996, Murphy et al. published the results of their national survey of hospital-based pharmacokinetics services. Altogether, 252 questionnaires were mailed to all respondents of the 1994 American Society of Health-System Pharmacists (ASHP) national survey of hospital-based pharmaceutical services " who indicated that their institution provided pharmacokinetics services. The response rate was 42.1% (n=106) however, only 98 surveys had complete data thus yielding a net response rate of 40.2%. Aminoglycosides were the main focus (60.8 27.7% of total) of pharmacokinetic consultations, followed by vancomycin (21.1 18.3%), theophylline (4.6 7.4%), other (3.6 16.0%), warfarin (3.1 11.1%), digoxin (2.2 6.1% ), phenytoin (l.2 3.0%), lithium... 

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