PHA 5127 Dose Optimization I Case Study IV 1. For the following situations, indicate whether the drug is: filtered, reabsorbed (if fully or if reabsorbed through transporters), or actively secreted (Assume GFR is 130mL/min, urine flow is 1.5mL/min) (1) Drug with fu= 0.3 and a Clren=39mL/min fu*GFR=0.3*130mL/min=39mL/min Clren= fu*GFR → filtered (2) Drug with fu=0.6 and a Clren=30mL/min fu*GFR=0.6*130mL/min=78mL/min Clren < fu* GFR → reabsorbed fu*urine flow=0.6*1.5mL/min=0.9mL/min (Clren>fu*urine flow) → not fully reabsorbed (3) Drug with fu=0.05 and a Clren=15mL/min fu*GFR=0.05*130mL/min=6.5mL/min Clren>fu* GFR → actively secreted (4) Drug with fu=0.2 and a Clren=0.3mL/min fu*GFR=0.2*130mL/min=26mL/min Clren<fu* GFR → reabsorbed fu*urine flow=0.2*1.5mL/min=0.3mL/min Clren=fu*urine flow → fully reabsorbed (5) Drug with fu=0.8 and a Clren=0.3mL/min fu*GFR=0.8*130mL/min=104mL/min Clren<fu* GFR → reabsorbed fu*urine flow=0.8*1.5mL/min=1.2mL/min (Clren<fu*urine flow) → reabsorbed through transporters 2. A 25 year old, 5’6’’, 80kg male patient with a serum creatinine concentration of 1.8mg/dL was given a drug treatment. Knowing this drug is mainly eliminated by glomerula filtration and has 60% plasma protein binding. Please estimate the Clearance of this drug (with Cockcroft-Gault equation) IBW=50kg + 2.3kg * 6=63.8kg TBW=80kg > 120%IBW=76.56 → This is an obese patient, so use ABW ABW= IBW+0.4*(TBW-IBW)=63.8 + 0.4*(80-63.8)=70.28kg GFR≈ CrCl = (140-age)*IBW/(72*serum creatinine)= (140-25)*70.28/(72*1.8)≈62.36mL/min=3.74L/hr CL=GFR*fu=3.74*(1-0.6)=1.496L/hr3. TRUE (T) or FALSE (F) For a high extraction drug, liver blood flow is important to both hepatic clearance and oral bioavailability. T F For low extraction drug, fu (fraction of unbound drug in plasma) is important to both hepatic clearance and oral bioavailability. T F Basic drugs that are polar in their unionized form, the extent of re-absorption depends on the degree of its ionization. T F Secretion is indicated when renal clearance is larger than GFR*fu. T F It is possible for renal clearance to be close to the kidney blood flow. T F Assuming no plasma protein binding, the renal clearance equals the urine flow when full reabsorption occurs. T
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