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PHARMACOKINETICS CLEARANCE CONCEPTS CLEARANCE CONCEPTS Know the meaning of linear pharmacokinetics/superposition! Calculate the ER for a drug with the concentration going into liver as 175mg/ml, and the concentration coming out of the liver as 125mg/min. Calculate CL H If fe=1 , what is the ER? A. 1 B. 0 C. Unable to determine D. 0.5 CLEARANCE CONCEPTS If the CL, total for a drug is 500ml/min, and fe is 0.75, calculate CL, hepatic: A. B. C. D. 375ml/min 50ml/min 125ml/min 200ml/min If a drug is 84% protein bound and the ER=0.25, is the drug exhibit restrictive or non-restrictive CL? If percent unbound vs plasma clearance is graphed, would restrictive or non-restrictive CL exhibit a linear relationship? If a drug is given orally and has a ER of 1 , how much of the original drug will make it to systemic circulation? RENAL CLEARANCE RENAL CLEARANCE Filtration clearance is… A. B. C. D. Non-restrictive Restrictive Combination of both Neither Secretion is… A. B. C. D. Non-restrictive Restrictive Combination of both Neither Glomerular filtration is a _____________ process, whereas secretion is a ____________ process. A. B. C. D. Active, active Active, passive Passive, passive Passive, active RENAL CLEARANCE What type of drug would mostly likely be reabsorbed? A. Bulky hydrophilic drug, fe=1 B. Small, lipid soluble drug, fe=0 C. Bulky, hydrophilic drug, fe=0 D. Small, lipid soluble drug, fe=0.9 If a drug is a weak base, and you give ammonium chloride, what will happen? A. Reabsorption will be enhanced B. Secretion will be diminished C. Elimination will be enhanced D. Elimination will be diminished RENAL CLEARANCE If a drug is a weak acid, which of the following will enhance elimination of the drug? A. Giving ammonium chloride B. Giving sodium bicarbonate If a patient is given too much of theophylline HCl, which of the following will enhance elimination? A. Giving ammonium chloride B. Giving sodium bicarbonate RENAL CLEARANCE Determine the renal clearance of the antibiotic. What is the probable mechanism for renal clearance of this drug? Age=28, BW=73 kg, CrCl=124 ml/min Antibiotic: F=90% Vd=0.31 L/kg t1/2=2.1 h Fup=0.77 67% of the antibiotic’s absorbed dose is excreted unchanged in the urine A. 84 ml/min, net tubular reabsorption B. 98 ml/min, net tubular secretion C. 84 ml/min, tubular secretion=tubular reabsorption D. 167 ml/min, no tubular secretion or tubular reabsorption (filtration only) RENAL CLEARANCE Captopril is a weakly basic drug that is used in the treatment of hypertension. Assume a glomerular filtration rate of 125ml/min. What are the mechanisms for renal clearance of captopril? A. Filtration only B. Reabsorption only C. Secretion only D. Filtration and net secretion E. Filtration and net reabsorption Extra info: CL=800 ml/min Fe=0.5 Vss: 0.81 L/kg Plasma protein binding: 75% RENAL CLEARANCE When cimetidine (a highly lipid soluble weak base that is highly secreted in the renal proximal tubules) and captopril are coadminstered, the renal clearance of captopril is reduced to approximately 125ml/min. What is the most likely mechanism to account for this reduction in renal clearance? A. Cimetidine reduces the filtration clearance of captopril B. Cimetidine enhances the reabsorption of captopril C. Cimetidine increases the unbound fraction of captopril D. Cimetidine blocks the renal secretion of captopril RENAL CLEARANCE Calculate the renal clearance for a patient: Total Body Weight= 56 kg Ideal Body Weight=60 kg Age=36 SCr=0.9 Gender=female RENAL CLEARANCE A patient with Chronic Kidney Disease (calculated CrCl=20ml/min) is given a drug with a CL of 140ml/min, fe=0.8, Calculate the clearance of the drug in this patient. RENAL CLEARANCE What is the primary concern with sustained low ef ficacy dialysis (SLED)? A. Patients are having increased concentrations of their medications that are renally cleared. B. There is no difference. C. Patients are being underdosed in their medications that are renally cleared. ENJOY YOUR FALL BREAK!