Vancomycin excretion

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. 

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 Clostridium difficile. Parenteral doses must be administered intravenously. A 1 hour intravenous infusion of 1 g produces blood levels of 15-30 jig/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 inflammation. Ninety percent of the drug is excreted by glomerular filtration. In the presence of renal insufficiency, striking accumulation may occur (Table 43-2). In functionally anephric patients, the... 

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.]... 

Vancomycin and teicoplanin are completely excreted unchanged in the urine by glomerular filtration. Vancomycin also partly undergoes hepatic metabolism. They are ototoxic and nephrotoxic. 

VANCOMYCIN ADEFOVIR DIPIVOXIL Possible t efficacy and side-effects Competition for renal excretion Monitor renal function weekly... 

ADEFOVIR DIPIVOXIL 1. ANTIBIOTICS -aminoglycosides, vancomycin 2. ANTICANCER AND IMMUNOMODULATING DRUGS - cidosporin, tacrolimus 3. ANTIFUNGALS-amphotericin, 4. ANTIPROTOZOALS-pentamidine 5. ANTIVIRALS - cidofovir, foscarnet sodium, tenofovir Possible t efficacy and side-effects Competition for renal excretion Monitor renal function weekly... 

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). 

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]. 

Monitor renal output to assure there is adequate volume of urine to excrete vancomycin. Monitor the white blood count to determine if vancomycin is effective. 

Medications whose excretion is primarily renal and for which there is evidence of age-related reduction in renal and total body clearance include (but are not limited to) amantadine, aminoglycosides, atenolol, captopril, cimetidine, digoxin, lithium, and vancomycin. Some hepatically metabolized medications can yield active, primarily renally excreted metabolites such as iV-acetylprocainamide, normeperidine, and morphine-6-glucuronide, which can accumulate with advancing age owing to reduced renal function. 

The usual duration of therapy for peritonitis associated with CAPD is 10 to 14 days, but up to 3 weeks of therapy may be required. Antimicrobial therapy should be continued until dialysate fluid is clear, cultures are negative for 2 to 3 days, and the patient is asymptomatic. When parenteral agents are administered, the initial dose would be the same as that for patients with normal renal function, whereas subsequent doses should be much less or given less frequently for renally excreted agents and should account for possible loss through peritoneal dialysis. Serum concentrations should be performed for aminoglycosides and vancomycin. Some studies have demonstrated that for patients with spontaneous bacterial peritonitis associated with cirrhotic ascites, treatment duration may be as short as 5 days when ascitic fluid polymorphonuclear cell counts are used to guide treatment. 

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. 

Vancomycin inhibits an early stage of cell-wall synthesis. It has a relatively narrow range of activity, but as yet, resistance is uncommon. Its use, excretion, and side effects are considered. 

Rybak MJ, Frankowski JJ, Edwards DJ, Albrecht LM. Alanine aminopeptidase and P2-n i-croglobulin excretion in patients receiving vancomycin and gentamicin. Antimicrob Agents Chemother ( 9Z1)3, 1461-4. 

A study in 10 patients with small cell bronchogenic carcinoma taking methotrexate found that when they were also given a range of oral anti-in-feetives (paromomycin, vancomycin, polymyxin B, nystatin) the urinary recovery of methotrexate was reduced by over one-third (from 69% to 44%). The paromomycin was believed to have been responsible. In another study the concurrent use of neomycin 500 mg four times a day for 3 days reduced the methotrexate AUC and the 72-hour cumulative excretion by 50%. In contrast, the same report suggests that kanamycin can increase the absorption of methotrexate, but no details are given. 

Delayed excretion and toxicity was seen when high-dose methotrexate was given to two patients recently treated with vancomycin. No significant interaction was found in eight other patients. 

Two patients treated with a chemotherapy regimen containing high-dose methotrexate, cisplatin, doxorubicin and ifosfamide had delayed methotrexate excretion and methotrexate toxicity during a cycle soon after they had received vancomycin. Methotrexate levels took 170 to 231 hours to fall to 200 micromol/mL, and toxicity (mucositis) occurred. Subclinical... 

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