So how do I dose thi s drug “X”
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So how do I dose thi s drug “X”. Timothy E Bunchman www.pcrrt.com [email protected]. ELIMINATION. I N P U T. Distribution. Re-distribution. D. “Known drug characteristics“. These recommendations made by panel of nephrologists and pharmacists Based on: Protein Binding Information - PowerPoint PPT Presentation
Transcript of So how do I dose thi s drug “X”
PHARMOCOKINETIC COMPARTMENTS
kidneybloodPeripheralliverGI Tract
Distribution Re-distribution
INPUT
ELIMINATION
D. “Known drug characteristics“
• These recommendations made by panel of nephrologists and pharmacists
• Based on:– Protein Binding Information– Volume of Distribution– Molecular Weight
When in doubt, start here…• Blood flow, filter type are not very important.• Find out
– In CVVHD: Dialysate flow rate (ml/hr)• Usually 2 L/1.73m2/hr (33 mL/1.73m2/min)
– In CVVH: Substitution Fluid rate (ml/hr)• Usually 2L/1.73m2/hr (33 mL/1.73m2/min)
• Add this to patient’s native Cr Cl (ml/1.73m2/min)• This is patient’s new Cr Cl dose accordingly• Works in most cases…is good enough for initial
estimates. Follow up with drug level monitoring.
Drug Prescribing in Renal Failureedited by George Aronoff et al
• Commonly carried text by pharmacists
• http://www.kdp-baptist.louisville.edu/renalbook/
• New edition to come out soon• Recommendations for new drugs• IHD and CRRT recommendations• Pediatric recommendations
Great so what do we really do?
• GENERAL PRINCIPLES– kinetics of drugs are based on therapeutic not toxic levels
(therefore kinetics may change)– choice of extracorporeal modality is based on availability,
expertise of people & the properties of the intoxicant in general
– Each Modality has drawbacks– It may be necessary to switch modalities during therapy
(combined therapies inc: endogenous excretion/detoxification methods)
Sieving Coefficients
Solute (MW) Convective Coefficient Diffusion Coefficient
Urea (60) 1.01 ± 0.05 1.01 ± 0.07
Creatinine (113) 1.00 ± 0.09 1.01 ± 0.06
Uric Acid (168) 1.01 ± 0.04 0.97 ± 0.04*
Vancomycin (1448) 0.84 ± 0.10 0.74 ± 0.04**
Calcium (protein bound) 0.67 + 0.1 0.61 + 0.07
Cytokines (large) adsorbed minimal clearance
*P<0.05 **P<0.01
Sieving Coefficient & Protein Binding
Drug Reported SC
Free Fraction
Amikacin 0.93 0.95Imipenem 0.78 0.80Metronidazole
0.84 0.80
Penicillin 0.68 0.50Ranitidine 0.78 0.85Vancomycin 0.80 0.90Valproic Acid 0.22 0.10
Vancomycin
• ~ 1500 Kda• ~ 75 % protein bind
Vancomycin clearance High flux dialysis membrane
0
50
100
150
200
250
0 3 12 15 27 30
Pt 1Pt 2
Time of therapy
Vanc
leve
l (
mic
/dl)
Rx Rx Rx
Rebound Rebound
Carbamazine
• ~ 1500 Kda• ~ 90 % protein bind
0
5
10
15
20
25
30
35
0 5 10 15 20 25 30 35 40
CBZ level(nl < 12)
High flux hemodialysis for Carbamazine Intoxication
Rx
Hrs from time of ingestion
Mic
/ml
Practical ideas
• If you can use a drug that can be monitored (eg vanco, aminoglycosides) then one can look at those kinetics, factor in the X drug molecular weight and protein binding then “best guess” the clearance
• Most vasopressor agents are cleared easily
Conclusion
• Until more data is obtained would err to “over dose” meds that are not nephrotoxic to avoid under dosing
