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So how do I dose thi s drug “X”

So how do I dose thi s drug “X”. Timothy E Bunchman www.pcrrt.com pcrrt@aol.com. 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

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So how do I dose thi s drug “X”

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  1. So how do I dose this drug “X” Timothy E Bunchman www.pcrrt.com pcrrt@aol.com

  2. ELIMINATION I N P U T Distribution Re-distribution

  3. D. “Known drug characteristics“ • These recommendations made by panel of nephrologists and pharmacists • Based on: • Protein Binding Information • Volume of Distribution • Molecular Weight

  4. 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.

  5. 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

  6. Great so what do we really do?

  7. 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)

  8. 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

  9. Sieving Coefficient & Protein Binding

  10. Vancomycin • ~ 1500 Kda • ~ 75 % protein bind

  11. Vancomycin clearance High flux dialysis membrane Rx Rx Rx Rebound Rebound Vanc level (mic/dl) Time of therapy

  12. Carbamazine • ~ 1500 Kda • ~ 90 % protein bind

  13. High flux hemodialysis for Carbamazine Intoxication Rx Mic/ml Hrs from time of ingestion

  14. Practical ideas • If you can use a drug that can be monitored (egvanco, 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

  15. Conclusion • Until more data is obtained would err to “over dose” meds that are not nephrotoxic to avoid under dosing

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