Aminoglycosides TDM

Question 1

PK Parameters (REVIEW)

Population PK parameters:
◦ T1/2: ~ 1.5-3 hrs
◦ Volume of distribution: ~ 0.26 L/kg
◦ K ~ 0.23 to 0.46 h-1

Answer 1

Oral absorption:
◦ Poor (must be given parenterally – intermittent IV infusion)

Distribution:
◦ Minimal protein binding (<5%), distributes to extracellular fluid

Metabolism:
◦ Minimal

Elimination:
◦ >90% unchanged in urine, approximates renal function

Question 2

Clinical Monitoring (REVIEW)

Answer 2

Amikacin has a higher therapeutic range
◦ Infection sites that are difficult to penetrate require higher target
◦ Lower target when used as a synergistic agent

Question 3

Adverse Effects (REVIEW)

Answer 3

Toxicities
◦ Ototoxicity (auditory and vestibular) - irreversible
◦ Nephrotoxicity (reduced glomerular filtration) – reversible

Question 4

Dosing Strategy: 2 options (REVIEW)

Answer 4

Extended Interval Dosing
1. Less toxic than
conventional dosing
2. Takes advantage of
concentration-dependent
killing (optimize
Cmax/MIC)
3. Cost savings
4. See contraindications

Conventional Dosing
1. Used in patient populations
contraindicated in
extended interval dosing
2. Synergy dosing (with betalactams for aerobic gramve infections or with
vancomycin for gram+ve
infections)

Question 5

Extended Interval Dosing

Answer 5

1) Calculate ideal body weight to determine the starting dose
◦ If actual body weight (ABW) < ideal body weight (IBW), use ABW
◦ If ABW > IBW by 20%, or BMI > 30 kg/m2 use dosing weight (DW)
◦ DW = IBW + 0.4 (ABW-IBW)
2) Draw post-infusion levels or use a nomogram (need to calculate
creatinine clearance) to verify dosing interval
3) Monitor efficacy: resolution of signs and symptoms
4) Monitor toxicity: renal and ototoxicity

Question 6

Hartford nomogram (7mg/kg) for
gentamicin and tobramycin

Answer 6

1. If the interval level falls in the areas marked as q24h, q36h, or
   q48h, the dosing interval should be every 24, 36, 48h respectively
2. If the interval level falls on one of the sloping lines, choose the
   longer interval
3. If above the q48h dosing interval area, DISCONTINUE extended
   interval dosing and switch to conventional dosing of
   aminoglycosides
4. If below the nomogram (i.e. < 2 mg/L), aminoglycoside
   dosing/therapy should be reassessed if patient not improving. A
   pharmacist consult is suggested.

Question 7

Precautions to extended interval dosing

Answer 7

1) Patients with chronic ascites or serious liver disease
2) Patients with auditory and vestibular disease
3) Pregnancy / post-partum (changes in volume of distribution)

Question 8

Contraindications to extended interval

dosing

Answer 8

1) Patients on dialysis
2) Aminoglycosides being used for synergy (use conventional dosing)
3) Abnormal clearance (e.g. burn patients > 20% body surface area)
4) Endocarditis
5) Surgical prophylaxis (use conventional dosing)