1. Dosage Regimen Design for Patients with Renal Insufficiency Pharmacy 732 Winter, 2001

2. Parameter Adjustment or “Q” Factor: Concept How much?

3. Q Factor: Where’s It Come From? Assuming nonrenal Cl is not changed by RF: Eq. 1

4. Q Factor: Where...? But Eq. 2

5. Q Factor: Where…? Since Cl R-N =fe  Cl T-N Eq. 3

6. Q Factor: Where…? Eq. 1 Eq. 2 Eq. 3

7. Q Factor: Where…?

9. Q Factor: Assumptions Know fe (normal renal function)  Cl R   GFR (i.e. CrCl) No change in Cl NR First-order kinetics One compartment model Metabolites not active/toxic

10. Q Factor: What Do You Do With It? Adjust dosage regimen (D, , or both) Adjusting D alone –D RF = D N  Q –Css similar, peak lower, trough higher Adjusting  alone –  RF =  N / Q –Css similar, peak similar, trough similar

11. Q Factor: What Do You…? Adjust both D and  –D RF = D N  Q   RF /  N –Css similar, peak and trough in-between

12. An Example: Ganciclovir Antiviral, normal dose = 5 mg/kg, dose interval = 12 hrs. Need to dose drug in patient with CrCl = 10 mL/min. What is Q factor?

13. or

14. What is the appropriate dosage regimen given this Q?

15. WARNING! Other kinetic parameters may also be altered by RF –Absorption –Distribution ( , ,  ) –Metabolism ( , ,  ) Always best to have literature for specific drug in renal failure patients Chapter 47 of DiPiro

16. Other Sources of Information Package insert Drug Information Handbook AHFS Drug Information Bennett