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

2. DistributionRe-distribution INPUTINPUT ELIMINATION

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 Failure edited by George Aronoff et al Commonly carried text by pharmacists http://www.kdp- baptist.louisville.edu/renalbook/ 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 ± 0.051.01 ± 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 + 0.10.61 + 0.07 Cytokines (large)adsorbedminimal clearance *P<0.05 **P<0.01

9. Sieving Coefficient & Protein Binding DrugReported SCFree Fraction Amikacin0.930.95 Imipenem0.780.80 Metronidazole0.840.80 Penicillin0.680.50 Ranitidine0.780.85 Vancomycin0.800.90 Valproic Acid0.220.10

10. Vancomycin ~ 1500 Kda ~ 75 % protein bind

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

12. Carbamazine ~ 1500 Kda ~ 90 % protein bind

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

14. 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

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