Transcript AK - 1-11

PHARMCOKINETICS
ALLIE PUNKE ([email protected])
VD/WEIGHT
• AMG
• VD= 0.3 L/kg
• Weight= Adjusted BW
• Vancomycin
• VD= 0.7 L/kg
• Weight= Total BW. Cap is usually 2 g
• B-Lactam
• VD= 0.3 L/kg
• Weight= Total BW
DISTRIBUTION
• Be able to generally recognize which antibiotics are
able to get into the CNS, lungs, and urine
DISTRIBUTION
• A patient with pneumonia is started on an
aminoglycoside for treatment. The team wants to
reach 10X the MIC of 1.5 mg/L. What blood
concentration would have to be targeted?
• 10 * 1.5= 15 mg/L
• BUT…<50% reaches the lungs, so 15*2= 30 mg/L
PK ALTERATIONS
• A patient is admitted to the ICU due to a serious
infection. The medical teams decides to start her on
Tobramycin. What PK parameter would you expect
to be altered in this patient?
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A. ka
B. Vd
C. CL (hepatic)
D. None would be altered
𝐷
𝐶=
𝑉
PK ALTERATIONS
• Which of the following antibiotics would you expect
to be primarily dependent on the liver for
clearance?
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A. Gentamicin
B. Linezolid
C. Amoxicillin/Clavulanic acid
D. Ciprofloxacin
PK ALTERATIONS
PHARMACODYNAMICS
• Be able to recognize what the antibiotic is
dependent on:
• 1. Concentration/Dose Dependent
• Peak: MIC ratio
• 2. Time/Exposure Dependent
• T > MIC
• 3. Hybrid/Blend
• AUIC
PHARMACODYNAMICS
• 1. Concentration Dependent Killing
• Examples: AMG, FQ
• 2. Time Dependent Killing
• Examples: B-Lactams
• 3. AUC/MIC
• Examples: Vancomycin
PHARMACODYNAMICS
• You designed a brand new drug that belongs to
the B-Lactam class. What is the preferred dosing
that would allow maximum killing?
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A. 2g Q24H bolus
B. 1g Q12H given over 3 hour infusion
C. 2g given over 24 hour continuous infusion
D. 1g Q12H bolus
PHARAMACODYNAMICS
• You designed a brand new drug that belongs to
the aminoglycoside drug class. What is the
preferred dosing?
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A. 100mg Q6H
B. 200mg Q12H
C. 400mg Q24H
D. 125mg Q8H
PHARMACODYNAMICS
PHARMACODYNAMICS
• Be able to recognize what percentage of T > MIC
should be based on the infection and the status of
the patient. Why is it not necessary to always be
100% above the MIC?
APPLICATION
• A previous healthy patient is started on a B-Lactam
antibiotic for a gram-negative infection. The
medical teams wants to maintain T > MIC above
75%. What is the best dosing regimen? K=0.231, Vd=
24 L, MIC=1.5
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A. 140 mg Q12H
B. 400 mg Q12 H
C. 80 mg Q8H
D. 125 mg Q12H
APPLICATION--SOLUTION
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400𝑚𝑔
=
24 𝐿
16.6 mg/L
3 hr
3 hr
ℎ𝑎𝑙𝑓 𝑙𝑖𝑓𝑒 =
3 hr
ln(2)
=3
0.231
hours
3 hr
• 16.6  8.33 4.16 2.08 1.041
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𝑇𝑖𝑚𝑒 𝑎𝑏𝑜𝑣𝑒 𝑀𝐼𝐶 3 ℎ𝑟 𝑡𝑖𝑚𝑒 𝑓𝑟𝑜𝑚 16.6→8.33 +3 ℎ𝑟 8.33→4.16 +3 ℎ𝑟 4.16→2.08
=
𝑇𝑜𝑡𝑎𝑙 𝑡𝑖𝑚𝑒
12 ℎ𝑜𝑢𝑟𝑠
75%
• This is, of course, only an estimation as part of the time from 2.08
1.041 the concentration will be above the MIC of 1.5.
• For a more exact answer, you can use the equation as mentioned in
class : C=C0e-kt. I got that in 10 hours, the concentration will reach the
MIC of 1.5. 10/12= 83%
APPLICATION
• A chemotherapy patient is admitted due to febrile
neutropenia and is started on a B-Lactam. The MIC
is 1, the half life is 4 hours, height is 5’7” and her
weight is 45 kg. What is the best dosing regimen?
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A. 50 mg Q24H
B. 140 mg Q24H
C. 120 mg Q12H
D. 30 mg Q12H
AMINOGLYCOSIDE DOSING
• A 70 year old man is admitted due to pneumonia.
The team wants to initiate Tobramycin.
Recommend a dosing regimen for the patient.
• 6’2” , 250 pounds, SCr=2.1 (Baseline=1.3)
• What weight to use?
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Extended or Conventional dosing?
If conventional, what peak concentration?
What dose?
How often to give?
AMINOGLYCOSIDE DOSING
Not necessary
to memorize.
You can derive
these
AMINOGLYCOSIDE DOSING
• You receive a consult to dose tobramycin for a
patient (BH- 56 kg, half-life~6 hours) with
bacteremia (MIC=0.5). Which of the following
dosing regimens would be best to provide efficacy
and prevent toxicity?
• A. Tobramycin 80 mg Q8H
• B. Tobramycin 100 mg Q 12H
• C. Tobramycin 400 mg Q 12H
AMINOGLYCOSIDE DOSING
• A 40 year old man is admitted due to endocarditis.
The team wants to initiate tobramycin. Recommend
a dosing regimen for the patient.
• 50 kg, SCr=0.8
• Blood cultures: 2/2 GPC
• What weight to use?
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Extended or Conventional dosing?
If conventional, what peak concentration?
What dose?
How often to give?
AMINOGLYCOSIDE DOSING
• A 35 year old patient is admitted to the hospital and
started on gentamicin for GNR in blood.
• Actual body weight: 65 kg, Ideal body weight: 75 kg
• SCr=0.6
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What weight to use?
Extended or Conventional dosing?
If conventional, what peak concentration?
What dose?
How often to give?
AMINOGLYCOSIDE DOSING
• A patient has been receiving Tobramycin 80 mg
Q12H for pneumonia with an organism with MIC:
0.5. The peak resulted as 3.9. What changes, if any,
would you like to make to the regimen?
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A. Increase the dose
B. Decrease the interval
C. Both A and B
D. No changes
AMINOGLYCOSIDE DOSING
• Remember:
• If use extended interval dosing, MUST use 7 mg/kg for
tobramycin and gentamycin OR 15 mg/kg for amikacin in
order to make a decision using the nomogram
• MUST get a serum drug concentration 6-14 hours to check
the interval
VANCOMYCIN—THE BASICS
• The dose is 1.75 g. How long should this be infused
over?
• What concentrations do we monitor for
vancomycin?
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A. Peak
B. Trough
C. Peak and Trough
D. Not always necessary to monitor concentration
VANCOMYCIN—THE BASICS
• Target trough for:
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Endocarditis
Meningitis
Cellulitis
Osteomyelitis
UTI
Pneumonia
Bacteremia
• When should a LD be given?
VANCOMYCIN
• A patient (80 kg) needs to be initiated on
vancomycin (half-life ~8 hours) for treatment of
endocarditis. Which dosing regimen would be best
to achieve efficacy and prevent toxicity?
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A. Vancomycin 1250 mg IV Q12 H
B. Vancomycin 2000 mg IV Q24 H
C. Vancomycin 1000 mg IV Q8 H
D. Vancomycin 1750 mg IV Q8 H
VANCOMYCIN
• A 65 year old woman is started on Vancomycin due
to a MRSA cellulitis infection.
• 5’10”, 80kg
• SCr=1.3
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What weight to use?
Loading dose?
Maintenance dose?
How often to give?
VANCOMYCIN
• A 63 year old male needs to be started on
Vancomycin. 6’1”, 85 kg, SCr=2 (Yesterday, SCr=1).
Select the best dosing regimen.
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A. 750 mg, re-dosed when level <20
B. 1,000 mg Q12H
C. 1,250 mg, re-dosed when level <20
D. 1,000 mg Q8H
VANCOMYCIN
• A patient with poor renal function is “pulsed” with
Vancomycin. The team wants to re-dose when the
level is less than 20. Two levels have been checked:
• 1/28 @ 11:00, level=45
• 1/29 @18:00, level=30
• When should you tell them to re-dose the
vancomycin?
QUESTIONS?
GOOD LUCK!