Download PK - 10-13

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?
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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…
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
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A.
B.
C.
D.
Non-restrictive
Restrictive
Combination of both
Neither
 Secretion is…
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

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?
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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?
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
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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?
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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
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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?
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A. Filtration only
B. Reabsorption only
C. Secretion only
D. Filtration and net secretion
E. Filtration and net reabsorption
 Extra info:
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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?
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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:
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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.
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