Aminoglycoside and Vancomycin Pharmacokinetics

  1. What is the volume of distribution of AGs?
    0.27 L/kg x DW (kg)
  2. What is the bioavailability of AGs?
    • Oral: poor
    • IM: good
  3. What is the primary site of distribution for AGs?
    • extracellular fluid:
    • ascitic
    • pericardial
    • peritoneal
    • pleural
    • synovial
    • abscesses
  4. How well do AGs penetrate the CNS?
    poorly and unpredictably
  5. What is the extent of AG protein binding?
  6. How are AGs metabolized?
    they're not
  7. How are AGs eliminated?
    • unchanged in the urine
    • primarily by glomerular filtration
    • 40-97% of a dose is excreted in 24h
    • readily removed by dialysis
    • ClAG (L/hr) = CrCl x 0.06
  8. What type of killing do AGs have?
    concentration-dependent killing
  9. What correlates best with clinical outcomes in AGs?
    peak concentrations
  10. What is the best correlation to toxicity in AGs?
    prolonged course (> 10d)
  11. What trough concentrations are correlated to AG toxicity?
    • > 2 mg/L gentamicin, tobramycin
    • > 10 mg/L amikacin
  12. What factors contribute to AG toxicity?
    • hypotension/shock/hypovolemia
    • advanced age
    • liver disease (leads to alteration in renal perfusion)
    • concurrent nephrotoxic agents
    • overdiuresis with diuretics
  13. What are the major toxicities associated with AGs?
    • ototoxicity
    • nephrotoxicity
  14. What weight is used to dose AGs?
    • dosing weight
    • DW = IBW + 0.4(TBW-IBW)
  15. When should a dosing weight be calculated for AGs?
    if TBW is > 30% over IBW
  16. What is the goal serum levels for AGs?
    • 4-10 mcg/ml tobramycin, gentamicin
    • 15-30 mcg/ml amikacin
  17. How should AGs be monitored?
    • peak and trough concentrations at steady state (on or after 3rd dose) if regimen is > 3-5d
    • trough within 30 minutes of the next dose
    • peak 30-60 minutes after end of infusion
  18. What are the goals of high-dose, extended-interval AG therapy?
    • optimize bactericidal activity
    • minimize toxicity
    • suppress expression of adaptive resistance
    • decrease costs
  19. How does high-dose, extended-interval dosing minimize toxicity?
    "drug-free" period at end of dosing interval allows AGs to diffuse out of the ears and liver back into the blood where levels are lower.
  20. Who should not receive high-dose, extended-interval AG dosing?
    • pregnant women
    • peds/neonates
    • burn patients (> 20% BSA)
    • severe liver disease
    • severe renal disease (CrCl < 30 ml/min)
    • bacterial endocarditis, osteomyelitis, or meningitis
    • neutropenic patients
    • cystic fibroseis patients
    • for synergy in staph or strep infections
  21. What is the initial dose of AGs in high-dose, extended-interval?
    • Hartford: 7 mg/kg
    • modified Hartford: 5 mg/kg
    • modified Hartford (Amikacin): 15 mg/kg
  22. How is the dosing interval determined for high-dose, extended-interval AG dosing?
    based on CrCl
  23. How should high-dose, extended-interval AG therapy be monitored and adjusted?
    a single serum concentration should be pulled 6-14h after start of therapy (7mg/kg nomogram) or end of the infusion (5 mg/kg nomogram)
  24. How should doses be rounded for gentamicin and tobramycin?
    to the nearest 20 mg
  25. How should doses be rounded off for amikacin?
    to the nearest 50mg
  26. What are the absorption characteristics of vancomycin?
    • oral: poor
    • IM: DO NOT administer IM
  27. How does vancomycin penetrate the CNS?
    poorly, but may be improved slightly with inflammation of the meninges
  28. How is vancomycin metabolized?
    it's not
  29. How is vancomycin eliminated?
    • unchanged in the urine
    • primarily by glomerular filtration
    • > 80% of dose is eliminated within 24h
    • not readily removed by dialysis (use high-flux membranes)
  30. What is the half-life of vancomycin in adults?
  31. What type of killing does vancomycin have?
    concentration-independent (maintain at 2-4x MIC)
  32. What is the goal peak concentration for vancomycin?
    20-60 mg/L (not generally monitored)
  33. What is the goal trough concentration for vancomycin?
    • 5-20 mg/ml (generally 10-15)
    • 15-20 mg/ml for pneumonia, osteomyelitis, septic arthritis, and meningitis
  34. What are the major toxicities for vancomycin?
    • ototoxicity
    • nephrotoxicity
    • red man's syndrome
  35. What peak concentrations are associated with ototoxicity?
    > 80 mg/ml
  36. What trough concentrations are associated with nephrotoxicity?
    > 15 mg/ml
  37. What are the risk factors associated with vancomycin toxicity?
    • advanced age
    • dehydration
    • pre-existing renal dysfx
    • pre-existing oto dysfx
    • co-administration of other nephro- or oto-toxic drugs
  38. What are the sx of redman's syndrome d/t vancomycin?
    • hypotension
    • flushing or rash on the face, neck, chest, and/or upper extremities
  39. How can you prevent red man's syndrome with vancomycin?
    slow infusion down to 15 mg/min or less and/or pre-medicate with an antihistamine
  40. How is vancomycin monitored?
    • trough-only
    • 30 min before administration
  41. What are the nomograms used for vancomycin dosing?
    • Detroit
    • Matzke
  42. How should vancomycin doses be rounded?
    to the nearest 250mg
Card Set
Aminoglycoside and Vancomycin Pharmacokinetics
Aminoglycoside and Vancomycin Pharmacokinetics