1. Dosage Adjustments for Aminoglycosides in Obese Patients Dennis Mungall, Pharm.D. Associate Professor, Pharmacy Practice Director, NTPD OSU,College of Pharmacy

2. Definition of Obesity  Percent Ideal Body Weight= (TBW x 100)/IBW  125-190% IBW is obese  >190% is morbid obesity  Also defined using Body Mass Index (BMI)  BMI= body weight(kg)/ Height squared (Meters)

3. Calculating Ideal Body Weight  IBW ( men) = 50 kg + 2.3 kg per inch >5ft  IBW ( females)=45.5 kg +2.3kg inch>5ft  BMI >=25 class III  The BMI correlates with disease risk

4. Alterations in Vd  Not all excess body weight in obese patients is adipose tissue  Increase in muscle mass and connective tissue constitute some of this mass  Adipose tissue does contain some water  Generally, Vd for hydrophillic drugs relates to lead body mass  Vd for lipophillic drugs relates better to total body weight

5. Alterations in Total Body Clearance  Increased fatty deposits and changes in hepatic enzymes are often seen in Obese subjects  Increases in glucuronidation, sulfation, and cytochrome P450 (CYP 2E1) have been documented. Decreases in activitiy CYP3A4 have been demonstrated.  Estimates of Creatinine clearance in the obese are different than the non-obese

6. Alterations in Renal Clearance  Some suggest using an estimate of Actual body weight for the Creatinine Clearance estimate: ABW =IBW +(C x (TBW-IBW) where C =.2-.4

7. Alterations in Renal Clearance (Salazar-Corcoran Amer J Med 1988;84:1053- 60) CrCl males = 2 (137-age) x {(0.285 x TBW}+(12.1xHT )) (51 x Serum Cr) CrCl females = 2 (146-age) x {(0.287 x TBW}+(9.74xHT )) (60 x Serum Cr)

8. Alterations in Renal Clearance Cockcroft- Gault Method Nephron 1976; 16:31-41  CrCl = (140-age) x IBW/72 x Crserum

9. Aminoglycoside  Mean Vd in normal, non overweight patients, is 0.26 Liters/Kg  ABW=IBW +(0.4 x (TBW-IBW)

10. Case Study With Gentamicin Mrs Jones is a 50 year old, 5 ft 6 inch, 150 kg patient Who develops Klebsiella Pneumonia while on a respirator In the Intensive Care Unit. Her serum creatinine is 1.7 mg/100cc.

11. Case Study With Gentamicin  Estimate the Loading dose to achieve a peak concentration of Gentamicin of 8 mg/l using ideal body weight, Total Body Weight, and Actual body weight  Estimate a maintenance dose of gentamicin to maintain this peak, given every 12 hours using the creatinine clearance methods of Cockcroft and Gault and Salazar. For Cockcroft and Gault use IBW, TBW, and ABW for this calculation. For Salazar method use Ht of 1.65 meters, for vd use IBW

12. Case Study With Gentamicin: Equations  Ke =.02 +.0028 CrCl -ke x tau  Dose = Ke x Vd x Cmax (1-e ) -ke x t ( 1-e ) Where : tau = 12 hours, Cmax = 8 mg/L, t= 1hour

13. Case Study With Gentamicin:Loading Dose MethodCalculated Wt VdLoading Dose IBW TBW ABW

14. Case Study With Gentamicin:Maintenance Dose MethodCrClKeDose C-GIBW C-GTBW CGABW Salazar