Vancomycin absorption

The answer is c. (Hardman, pp 887, 889.) Bile acid-binding resins bind more than just bile acids, and binding of simvastatin to cholestyramine is the most likely mechanism for decreased Gl absorption. Cholestyramine may also bind to several other drugs, including digoxin, benzothiadiazides (thiazides), warfarin, vancomycin, thyroxine (T4), and aspirin. Medications should be given one hour before or four hours after cholestyramine. 

Absorption/Disthbution - Systemic absorption of oral vancomycin is generally poor. 

Prasad, Y.V., et al. 2003. Enhanced intestinal absorption of vancomycin with Labrasol and D-alpha-tocopheryl PEG 1000 succinate in rats. Int J Pharm 250 181. 

Infections limited to soft tissue will require between 7 and 10 days of intravenous therapy followed by an additional 14 days of oral therapy (total duration 2-4 weeks). If MRSA is isolated, intravenous vancomycin must not be switched to oral vancomycin which has negligible absorption from the gastrointestinal tract. Oral agents may be selected from rifampicin, tetracyclines, fusidic acid or trimethoprim depending on sensitivity data and a combination of two agents is recommended. Oral linezolid monotherapy is an effective alternative. 

ANION EXCHANGE RESINS VANCOMYCIN (ORAL) 1 vancomycin levels Inhibition of absorption Separate doses as much as possible... 

Because of its potential toxicity, vancomycin is reserved for serious infections in which less toxic antibiotics are ineffective or not tolerated. Generally, vancomycin is administered intravenously because of poor intestinal absorption. It is the drug of choice for treating infections caused by methicillin-resistant staphylococci and penicillin-resistant Streptococcus pneumoniae. Vancomycin has been used to treat enterococcal infections because of their resistance to the P-lactam antibiotics, but most enterococci are now also resistant to vancomycin. Oral administration of rancomycin is important for treatment of some gastrointestinal infections such as pseudomembranous colitis caused by C. difficile. 

Antihistamines (Hi receptor antagonists) prevent anaphylactoid reactions to vancomycin (16). The recommended method of administration is by intravenous infusion of a solution of 0.25-0.5% over 60 minutes, and patients have to be monitored closely. A possible red man syndrome has also been associated with systemic absorption of oral vancomycin in a patient with normal renal function (17). 

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. 

Thompson CM Jr, Long SS, Gilligan PH, Prebis JW. Absorption of oral vancomycin—possible associated toxicity. Int J Pediatr Nephrol 1983 4(l) l-4. 

Vancomycin is poorly absorbed after oral administration. However, in patients with normal renal function, low concentrations of vancomycin have been demonstrated in the urine indicating some systemic absorption even by this route. For systemic gram positive infections, vancomycin is administered intravenously. The peak serum levels of vancomycin are approximately proportional to the dose given. For example, intravenous administration of 500 mg of vancomycin to normal volunteers resulted in serum levels of 2 to 10 mg/L two hours after the dose. After 1000 mg or 2000 mg of vancomycin are given, two hour serum levels approximate 25 mg/L and 45 mg/L, respectively [184]. 

Inhibiting the activity of urease-producing bacteria by using neomycin, metronidazole, or vancomycin can decrease production of ammonia. Neomycin at doses of 2 to 8 g daily in divided oral doses results in clinical improvement in as many as 80% of patients. At these doses, however, absorption is 1% to 5% and can result in irreversible ototoxicity and nephrotoxicity. As such, even though efficacy is equivalent to lactulose, neomycin should not be first-line therapy. Metronidazole produces response rates similar to neomycin, but side effects, particularly gastrointestinal, limit its use. In patients... 

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 is a high-molecular-weight polypeptide and teicoplanin is similar in structure and, in fact, is a complex of five related compounds. Both are poorly lipid-soluble. For both compounds, absorption after oral dosing is slight/absent, a property relating to the low lipid solubility and polypeptide structure, as they are broken down to constituent amino acids in the GIT. Teicoplanin is well absorbed after intramuscular dosing, and has a prolonged half-life in humans of 45-70 h. Vancomycin... 

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. 

Recent work utilizing ultraviolet absorption techniques has shown that vancomycin and ristocetin bind in cell-free systems to mucopeptide precursors in equimolar proportion and that the D-alanyl-D-alanine moiety of the peptide is required for the binding reactionl . Penicillin, considered an analogue of acyl-D-alanyl-D-alanine , also modifies the absorption spectrum of vancomycin . Studies on binding of Sj. anco-mycin in intact bacteria have confirmed the results on binding to cell-walls... 

Pogue JM, DePestel DD, Kaul DR, Khaled Y, Frame DG. Systemic absorption of oral vancomycin in a peripheral blood stem cell transplant patient with severe graft-versus-host disease of the gastrointestinal tract. Transpl Infect Dis 2009 11(5) 467-70. 

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