Download 1 PHA 5127 Homework 4 1. What is the maximum extraction ratio for

PHA 5127
Homework 4
1.
What is the maximum extraction ratio for renal filtration if neither reabsorption nor
active secretion take place? Explain.
2.
The renal clearances and the fractions unbound to plasma proteins of three drugs in a
70kg 40 year old man are listed as follows:
Renal Clearance (ml/min)
Drug 1
62.5
Drug2
30
Drug3
0.45
Fraction Unbound
0.5
0.01
0.3
Explain the likely contribution of filtration, secretion, and reabsorption to the renal handling of
each of these drugs. Assume a GFR of 125 ml/min and a urine flow of 1.5 ml/min.
3.
A 5'10" 40 year old 90kg man has a serum creatinine level of 1.5 mg/100 ml and is being
treated with aminoglycosides. Estimate the clearance for the aminoglycoside and the half-life for
this patient. If the desired peak plasma level is 6 mg/L and the volume of distribution is 0.24
L/kg (IBW), what dose should be given (just consider one dose). How long will it take to reach a
plasma level of 1 mg/L.
4.
What are the assumptions made by the one-compartment model?
5.
Mark the following statements true (T) or false (F):
TF
TF
The maximum value which renal clearance can approach is 1200 ml/min.
Large drug molecules and low degree of protein binding could predispose a drug
to glomerular filtration.
TF
Tubular secretion may be a competitive process.
TF
Tubular reabsorption can only be a passive transport process.
TF
Highly ionized drugs tend to have more tubular reabsorption.
TF
Molecular size, protein binding, and lipid solubility significantly influence
glomerular filtration.
TF
Urinary excretion of amphetamine can be decreased by raising pH.
TF
With first-order elimination, the fraction of a drug in the body eliminated over a
given time depends on the drug concentration.
D:\Homeworks\Homework4\Fall-99\hw-4-99.doc
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Use the Excel Spreadsheets available to draw the Cp vs time curves for the following inputs. Use
the IV-S.xls for the first two (one compartment, i.v. bolus, single dose) and Oral.xls for the third
(one compartment, oral, single). Calculate and record the missing parameters and explain the
results.
1.
2.
Input
D[mg]
Vd(L)
CL(L/h)
120
100
12
120
100
24
Input
D[mg]
Vd(L)
CL(L/h)
Results
Peak(mg/L)
Ke(1/h)
t1/2(h)
AUC
Results
180
100
24
60
100
24
D:\Homeworks\Homework4\Fall-99\hw-4-99.doc
Peak (mg/L)
Ke(1/h)
t1/2 (h)
AUC(mg/L*h)
2
3.
Input
D[mg]
Bioavail.
Ka(1/h)
Vd(L)
CL(L/h)
60
1
1
50
20
Results
tmax (h)
Peak(mg/L)
Ke(1/h)
t1/2 (h)
AUC(mg/L*h)
60
1
1
100
20
D:\Homeworks\Homework4\Fall-99\hw-4-99.doc
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