Allie punke (apunke@uthsc.edu) pharmcokinetics Allie punke (apunke@uthsc.edu)

Vd/weight AMG Vancomycin B-Lactam VD= 0.3 L/kg Weight= Adjusted BW Weight= Total BW. Cap is usually 2 g B-Lactam 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? A. ka B. Vd C. CL (hepatic) D. None would be altered 𝐶= 𝐷 𝑉 B. Giving fluids  increased Vd.

PK Alterations Which of the following antibiotics would you expect to be primarily dependent on the liver for clearance? A. Gentamicin B. Linezolid C. Amoxicillin/Clavulanic acid D. Ciprofloxacin D  Ciprofloxacin is more lipophilic, therefore requires the liver to undergo metabolism/CL to make it more hydrophilic

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 AUC/MIC is the sum of the AUCs in 24 hours divided by the MIC

pharmacodynamics You designed a brand new drug that belongs to the B-Lactam class. What is the preferred dosing that would allow maximum killing? A. 2g Q24H bolus B. 1g Q12H given over 3 hour infusion C. 2g given over 24 hour continuous infusion D. 1g Q12H bolus C. Continuous infusion is technically better because it allows more TIME above the MIC. Not very realistic to do in a hospital, though.

pharamacodynamics You designed a brand new drug that belongs to the aminoglycoside drug class. What is the preferred dosing? A. 100mg Q6H B. 200mg Q12H C. 400mg Q24H D. 125mg Q8H C. Concentration dependent killing. Want high peak: MIC.

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? Due to postantibiotic effect and immune system!

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 A. 140 mg Q12H B. 400 mg Q12 H C. 80 mg Q8H D. 125 mg Q12H B

Application--solution 400𝑚𝑔 24 𝐿 = 16.6 mg/L ℎ𝑎𝑙𝑓 𝑙𝑖𝑓𝑒= ln⁡(2) 0.231 =3 hours 16.6  8.33 4.16 2.08 1.041 𝑇𝑖𝑚𝑒 𝑎𝑏𝑜𝑣𝑒 𝑀𝐼𝐶 𝑇𝑜𝑡𝑎𝑙 𝑡𝑖𝑚𝑒 = 3 ℎ𝑟 𝑡𝑖𝑚𝑒 𝑓𝑟𝑜𝑚 16.6→8.33 +3 ℎ𝑟 8.33→4.16 +3 ℎ𝑟 4.16→2.08 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% 3 hr 3 hr 3 hr 3 hr

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? A. 50 mg Q24H B. 140 mg Q24H C. 120 mg Q12H D. 30 mg Q12H C

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? Extended or Conventional dosing? If conventional, what peak concentration? What dose? How often to give? IBW=82.2 kg Adjusted= 94.5 kg CrCl=Technically 43, but currently in AKI About 220 mg (2.5*94.5 kg). Check level with morning labs and redose when level <2

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 B

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? Extended or Conventional dosing? If conventional, what peak concentration? What dose? How often to give? Synergy conventional dosing only! Peak concentration: 3-4 Dose: 60 mg Ever 8 hours

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 What weight to use? Extended or Conventional dosing? If conventional, what peak concentration? What dose? How often to give? Actual Extended 7* 65=460mg daily *Must follow up* Use Hartford nomogram to check dose after 6-14 hours to check interval

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? 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? A. Peak B. Trough C. Peak and Trough D. Not always necessary to monitor concentration 1 gram/hour, so 1 hour and 45 minutes 15-20 for most, except UTI, cellulitis

Vancomycin—The Basics Target trough for: 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? 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 What weight to use? Loading dose? Maintenance dose? How often to give? Total Body weight (80kg) Doesn’t mention patient is in shock, so no MD=15*80=1200 mg Probably Q24 H

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. 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 C

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? 31 hours after 1/29 @18:00 (1/31 @1:00)

Questions? Good luck!