PHAR 7633 Fall 1999

Pharmacokinetics

OU HSC College of Pharmacy

Second Exam 12 November 1999

Section FOUR. 15 + 19 + 10 = 44 points

Show all your work for full credit. All material not deleted or crossed-out will be considered for grading. Do NOT use any linear or semi-log regression functions/features that might be on the calculator that you use during this exam.

Q4.1 Version A, D, Q4.2 Version B, Q4.3 Version C (15 points) Assuming a one compartment linear pharmacokinetic model, with kel = 0.16 hr-1 and V = 78 L, calculate the expected plasma concentration at 24 hours after the following IV bolus dose schedule: 200 mg at time 0 hr; 300 mg at 6 hr; 300 mg at 18 hours.

Parameter

A

B

C

D

kel
0.16
0.07
0.34
0.09
V
78
321
26
234
Dose1
200
100
300
100
Dose2
300
200
200
400
t2
6
6
6
6
Dose3
300
300
300
200
t3
18
18
12
12
Cp (mg/L)
1.74
0.85
0.22
0.68

Q4.2 Version A, D, Q4.3 Version B, Q4.1 Version C. (19 points) Calculate an appropriate dosing regimen for the following male patient; age = 67 years, weight = 74 kg, serum creatinine = 1.8 mg/ 100 ml (mg %). With this drug the kel is a function of creatinine clearance and previously determined values include: kel = 0.05 hr-1 with CLCr = 15 ml/min and kel = 0.12 hr-1 with CLCr = 60 ml/min. The apparent volume of distribution was 0.45 L/kg. Develop a dosing regimen to keep the peak concentration close to but below 6 µg/ml and the trough concentration below 1 µg/ml. Adjust tau to an appropriate value that is a multiple of 4 hours. Round doses to the nearest, appropriate 5 mg and calculate the expected maximum and minimum plasma concentrations.

Parameter
A
B
C
D
Sex
M
F
M
F
Age
67
65
45
55
Weight
74
68
78
75
SCr
1.8
1.7
1.2
1.1
CLCr (ml/min)
41.7
35.4
85.8
68.4
kel1
0.05
0.04
0.05
0.05
CLCr1
15
15
15
15
kel2
0.12
0.15
0.19
0.15
CLCr2
60
60
60
60
knr
0.0267
0.0033
0.0033
0.0167
b
0.00156
0.00244
0.00311
0.00222
kel
(hr-1)
0.0915
0.0899
0.270
0.169
V
0.45
0.25
0.3
0.22
Cpmax
6
8
8
6
Cpmin
1
1
0.5
0.5
R
0.167
0.125
0.0625
0.0833
tau (hr)
19.6
23.1
10.3
14.7
tau' (hr)
20
24
12
16
R'
0.160
0.116
0.0391
0.0673
MDose (mg)
168
120
180
92.3
LDose (mg)
200
136
187
99
MD' (mg)
165
120
175
90
LD' (mg)
195
135
185
95
Cpmax' (mg/L)
5.90
7.98
7.78
5.85
Cpmin' (mg/L)
0.947
0.923
0.304
0.393
Cpmax' (mg/L)
5.86
7.94
7.91
5.76

Q4.3 Version A, D, Q4.1 Version B, Q4.2 Version C. (10 points) A drug is to be given orally every twenty four hours to achieve an average concentration of 30 mg/L. Calculate the dose (F = 0.80) required if t1/2 = 12 hours and V = 32 L. Round your answer to the nearest 25 mg. Estimate the average, peak and trough concentrations after steady state is reached, using the rounded dose.

Parameter
A
B
C
D
Tau
24
12
12
24
Cp(bar)
30
15
20
25
F
0.8
0.9
0.7
0.8
t1/2
12
16
7
12
kel
(hr-1)
0.058
0.043
0.099
0.058
V
32
123
15
27
Dose (mg)
1664
1066
509
1170
Dose' (mg)
1675
1075
500
1175
Cp(bar) (mg/L)
30.2
15.1
19.6
25.1
Cpmin (mg/L)
14.0
11.5
10.2
11.6
Cpmax (mg/L)
46.5
18.7
29.1
38.6

This file was last modified:
Copyright 1999 David W.A. Bourne