20. CPK OF AMINOGLYCOSIDES

Question 1

What is the traditional dosing LD range for gentamicin & tobramycin?

Answer 1

2 to 2.5 mg/kg

Question 2

What is the traditional dosing MD range for gentamicin & tobramycin?

Answer 2

1.5 - 2 mg/kg every 8-12 hours
(normal KF)

Question 3

Why would a LD be used?

Answer 3

to get to effective concentration faster

Question 4

What PK should be used to calculate initial dosing regimen?

Answer 4

population PK

Question 5

List the steps in the stepwise approach of aminoglycoside (AG) dosing

Answer 5

1. Select desired Cmax & Cmin
2. Calculate correct modified pt weight
3. Estimate CrCl
4. Calculate the population estimate for k
5. Calculate the population estimate for t1/2
6. Calculate the population estimate for Vd (V = 0.325 L/kg)
7. calculate the population estimate for tau (dosing interval)
8. Calculate the maintenance dose (MD), in mg, using the desired Cmax
9. Calculate actual Cmax & Cmin (always double check your calculations !!!)

Question 6

In general, should you round to the longer or shorter dosing interval?

Answer 6

longer dosing interval

Question 7

How should the MD be rounded?

Answer 7

to the nearest 10-20 mg

Question 8

What weight should be used to calculate V?

Answer 8

• TBW (if TBW ≤ IBW)
• IBW (if TBW < 1.3xIBW)
• AdjBW if obese (TBW ≥ 1.3xIBW) or morbidly obese (BMI ≥ 40 kg/m 2)

Question 9

Why would extended-interval AG dosing be used?

Answer 9

• Larger doses are given less frequently (Maximizes peak/MIC ratio)
• Give dose q24h to patients with normal renal function to minimize accumulation in target organs
• Best for ppl with close to or normal renal function

Question 10

What is the common extended-interval AG dosing for gentamicin & tobramycin?

Answer 10

5-7 mg/kg as a single dose (7 most common)

Question 11

What body weight should be used for extended-interval AG dosing?

Answer 11

• TBW if < IBW
• IBW if TBW < 1.3xIBW
• AdjBW if TBW ≥ 1.3xIBW

Question 12

What graph can be used to estimate an extended-interval AG dosing regimen?

Answer 12

Hartford Nomogram

Question 13

According to the Hartford Nomogram, when is a common initial dose for extended-interval AG dosing?

Answer 13

• 7 mg/kg infused over 1 hour
• Target Cmax → 20 ug/mL
• Cmax/MIC ratio 10:1 (assuming MIC is 2ug/mL)

Question 14

Based on pt CrCl, what CrCl indicates the need for traditional AG dosing?

Answer 14

< 20 mL/min

Question 15

What is the recommended target peak for traditional AG doing in a pt with moderate infection / disease?

Answer 15

4-6 ug/mL

Question 16

What is the recommended target peak for traditional AG doing in a pt with moderate-severe infection / disease?

Answer 16

6-8 ug/mL

Question 17

What is the recommended target peak for traditional AG doing in a pt with severe infection / disease?

Answer 17

8-10 ug/mL

Question 18

Do trough concentrations change for traditional AG dosing based on severity of disease / infection?

Answer 18

NO!
< 1 across all infections

Question 19

What AG is used for gram-positive infections?

Answer 19

Gentamicin
target peak - 3-5 ug/mL
same trough (< 1)

Question 20

What is the Cmax for gentamicin & tobramycin in extended-interval AG dosing?

Answer 20

15-20 μg/mL

Question 21

What is the trough for gentamicin & tobramycin in extended-interval AG dosing?

Answer 21

undetectable (“below the detection limit of the assay”)

Question 22

Explain how traditional AG dosing is monitored

Answer 22

• Renal function daily
• Infection based parameters
• AG concentration
• Calculate PATIENT SPECIFIC PK parameters for k and V
• Adjust dose based on PATIENT SPECIFIC parameters

Question 23

Explain how AG concentrations should be obtained for traditional AG dosing monitoring

Answer 23

• At steady state (can estimate based on 4-5 t1/2) or earlier if necessary
• Obtain peak & trough concentrations (usually 3-4 doses)

Question 24

Explain how AG PEAK & TROUGH concentrations should be obtained for traditional AG dosing monitoring

Answer 24

• Peak concentrations should be obtained at least 0.5 hours after the end of a 0.5-hour infusion (after distribution phase is complete)
• Trough concentrations should be obtained ≤ 0.5 hours before the next dose

Question 25

Explain the options for follow-up when using the Hartford Nomogram

Answer 25

1: Obtain 2 concentrations after the start of the first infusion (around 2 hr and 10 hr after infusion - for normal function), then calculate PK parameters & use them to make pt specific adjustments 2: Serum concentration monitoring - Obtain single blood sample 6-14 hours after start of infusion on day 5, (this sample is often referred to as a “random” sample), then use nomogram to determine appropriate dosing interval (if serum conc is off nomogram, must estimate Cmax & Cmin)