Pharmaceutics III - PHAR 4634

Homework #6

Answers

1. First calculate A, B, , and .

2.696

hr-1

0.104

hr-1

A

1.142

mg/L

B

1.142

mg/L

Use Cp = A * e- * t + B * e- * t with > to calculate Cp at each time point. Thus:

Time(hr)

Cp (mg/L)

0

2.28

0.25

1.69

0.5

1.38

1

1.11

2

0.93

4

0.75

6

0.61

8

0.50

10

0.40

12

0.33

Linear Plot

Semi-log Plot

2. First graph the data:

Dose 200 mg by IV Bolus

Time (hr)

Concentration (mg/L)

0.25

14.8

0.5

12.1

1

8.8

2

6.0

4

4.0

6

2.2

8

1.4

10

0.91

12

0.55

Semi-log Plot

Initial Parameters

A

9.100

mg/L

B

8.789

mg/L

1.52646

hr-1

0.22948

hr-1

Converted Parameters

k21

0.867

hr-1

kel

0.404

hr-1

k12

0.485

hr-1

Vc

11.2

L

Varea

19.7

L

3. Using a dosing interval close to the terminal half-life. Half-life (t1/2) = ln(2)/0.14 = 4.95 hr. Using a dosing interval (tau) of 4, 6, or 12 hours gives:

0.14

0.14

0.14

hr-1

Varea

32.8

32.8

32.8

L

F

0.85

0.85

0.85

Cbar

15

15

15

mg/L

Tau

4

6

12

hr

Dose

324.1

486.2

972.4

mg

Dose'

325

475

975

mg

Cbar'

15.04

14.65

15.04

mg/L

4. Using the noncompartmental approach

Dose (iv)

200

mg

AUC (iv)

87.5

mg.hr.L-1

AUMC (iv)

745

mg.hr2.L-1

Dose (po)

500

mg

AUC (po)

116.74

mg.hr.L-1

AUMC (po)

1095

mg.hr2.L-1

MRT (iv)

8.514

hr

MRT (po)

9.380

hr

MAT (po)

0.866

hr

k' (iv)

0.117

hr-1

ka' (po)

1.155

hr-1

CL (iv)

2.286

L.hr-1

F (po)

0.534

Vss

19.5

L