Case Study 1
Spring 2009
100 mg of a drug are given i.v. and p.o. to the same patient. The following
plasma level concentrations are measured.
C
p
C
p
Time [hrs] i.v.[µg/ml] oral [µg/ml]
0.2 2.58 0.30
0.6 2.40 0.74
1.0 2.24 1.18
2.0 1.90 1.26
3.0 1.60 1.22
4.0 1.34 1.10
6.0 0.96 0.82
8.0 0.68 0.58
12.0 0.34 0.30
1. Determine the absolute bioavailability of the oral product.
2. From the above data calculate the clearance and Vd.
3. From the above data, how do we know that the terminal slope of the oral dose is the
elimination rate constant (ke) and this is not a flip flop situation?
4. K.L., a 85 kg male smoker with chronic obstructive pulmonary disease, is to be started
on an oral regimen of aminophylline (85% of which is theophylline). The
pharmacokinetic parameters for this patient are Vd (0.5 L/kg), CL (80 mL/h/kg) and F
(1.0).
Design an oral dosage regimen of aminophylline (100- and 200 mg tablets are marketed)
for this patient to attain and maintain a plasma concentration within the therapeutic range
(10-20 μg/ml) and an average steady state target of 15mg/L. The absorption of
theophylline is complete and rapid.
5. How will the following parameters change for a drug that is a high extraction drug
eliminated by hepatic clearance only if the free fraction in plasma is changed from 0.8 to 0.2.
Indicate increase, decrease, or remain the same.
A. Vd
B. EH
D. CL
E. K
e
