17 views

Uploaded by sedalatianz

non parametric

non parametric

© All Rights Reserved

- Calculations used to determine patient-specific doses “The right dose”
- CTD Guidance -Final
- Anvisa Ba-be Guidelines
- B. Pharm.-ivth Year Syllabus (3)
- Harvoni
- Effect of Food on Pharmacokinetics of Meloxicam_ijsit_2.3.7
- 1997 PharmacolRev 49 403 Lin
- Oxindoles and Their Pharmaceutical Significance- an Overview
- art04
- Quantifying CA Absorbtion
- Comite de Expertos LME OMS 2015
- clinical_chemistry_at_ummc_and_vamc.pdf
- 156-288-2-PB
- The Sex Influence on Pharmacokinetic
- IVT Completion Form
- Ibrucent 140 Capsule 90
- seminer.......BP
- Dr Ankit's Complete List of Drugs and Consumables for Liver Transplant Case
- 13
- life or death

You are on page 1of 11

return to the Course index

previous | next

o AUMC (area under the first moment curve)

o MRT (mean residence time)

o MAT (mean absorption time)

o MDT (mean dissolution time)

Non compartmental methods can be used to determine certain pharmacokinetic parameters

without deciding on a particular compartmental model. The basic calculations are based on the

area under the plasma concentration versus times curve (zero moment) and the first moment

curve (AUMC). The AUC can be calculated as before using the trapezoidal rule. The first

moment is calculated as concentration times time (Cp t). The AUMC is the area under the

concentration times time versus time curve. Maybe best covered with an example. Consider a

drug given both by IV and oral administration. Both the AUC and AUMC were calculated using

the trapezoidal rule without making any assumption concerning the number of compartments.

The final segment of the AUC curve is calculated as Cp(last)/k', where k' is the last exponential

term (the slowest) calculated from the Cp versus time graph. The last segment for the AUMC

curve is:

Bolus Administration

Time

Cp

Cp t

AUC

AUMC

(hr) (mg/L) (mg.hr/L)

(mg.hr/L)

(mg.hr2/L)

0

8

0

0

0

1

7.09

7.09

7.55

3.55

2

6.29

12.58

14.24

13.39

3

5.58

16.74

20.18

28.05

4

4.95

19.80

25.45

46.32

6

3.89

23.34

34.29

89.46

9

2.71

24.39

44.19

161.06

12

1.89

22.68

51.09

231.67

18

0.92

16.56

59.52

349.39

24

0.44

10.56

63.60

430.75

67.27

549.31

These data, Cp versus time and Cp x time versus time, can be plotted on linear graph.

Equation 20.1.5 Equation for Apparent Volume of Distribution, Steady State (Vss)

From the AUC and AUMC values we can calculate the mean residence time, MRT. This is the

average time that the drug stays in the body (or plasma as measured here). It can be related to the

average elimination rate constant as 1/MRT. The values from the above data are

MRT = 549.31/67.27 = 8.17 hr

and

kel' = 1/8.17 = 0.12 hr-1

Remember we can also calculate the clearance,

CL = Dose/AUC = 100/67.27 = 1.49 L.hr-1

Finally a steady state volume can be calculated as

Table 20.1.2 Typical Cp versus Time Data after 250 mg Oral Administration

Time (hr) Cp (mg/L)

Cp t (mg.hr/L)

AUC (mg.hr/L)

AUMC (mg.hr2/L)

0

0

0

0

0

1

12.18

12.2

6.09

6.09

2

14.12

28.24

19.24

26.30

3

13.43

40.29

33.02

60.57

4

12.16

48.64

45.82

105.04

6

9.64

57.84

67.62

211.52

9

6.73

60.57

92.18

389.14

12

4.69

56.24

109.31

564.42

18

2.28

41.22

130.25

856.92

24

1.11

26.64

140.45

1060.50

149.70

1359.58

These data, Cp versus time and Cp x time versus time, can be plotted on linear graph.

and additional parameters can be calculated (NOTE: We don't calculate Clearance or Vss using

oral data).

The data were calculated after a 250 mg oral dose of the same drug. From these data a MRT was

calculated as

MRT = AUMC/AUC = 1361/149.8 = 9.08 hr

We can subtract from this MRT(PO) the MRT(IV) to get an idea of the absorption process, the

mean absorption time (MAT). That is

MAT = MRT(PO) - MRT(IV) = 9.08 - 8.17 = 0.92 hr

ka' = 1/MAT = 1/0.92 = 1.09 hr-1

Of course we can calculate the bioavailability of the oral dosage form using the dose adjusted

AUC ratio. Thus

F = (149.70/67.27) x (100/250) = 0.89

Another Example

using Data from Bevill et al. 1977

Pharmacokinetics of Sulfamethazine in Cattle following IV and Three Oral Dosage Forms

Dosage Forms

IV

Solution

Tablet

Slow Tablet

AUC

AUMC

MRT (hr)

MAT (hr)

437

6393

14.6

431

9454

21.9

7.3

450

11303

25.1

10.5

765

45484

59.5

44.9

MDT (hr)

3.2

37.6

Rate Constant (hr-1) Non Linear Regression Analysis

Non Compartmental Analysis

kel'

0.077

0.068

ka'

0.11

0.14

kd' (fast)

0.41

0.31

kd' (slow)

0.026

0.027

Non compartmental analysis:

kel' = 1/MRT

ka' = 1/MAT

kd' = 1/MDT

where MDT is the mean dissolution time

Want more practice with this type of problem!

References

Bevill, R.F., Dittert, L.W. and Bourne, D.W.A. 1977 Pharmacokinetics of Sulfamethazine

in Cattle following IV and Three Oral Dosage Forms, J. Pharm. Sci., 66, 619-23

previous | next

2015 at 09:21 PM

Non compartment Analysis IV Administration

A drug follows first order (i.e. linear) pharmacokinetics. A 200 mg dose was given by

rapid IV administration to a patient and a number of plasma drug concentration

were determined. The results are shown in the table below. A non compartmental

analysis was completed and AUC and AUMC values calculated. As you can see some

of these values are missing from the table. Complete the table and estimate MRT,

CL, and Vss from these data.

Time

hr

Cp

mg/L

AUC

mg.hr/L

AUC

mg.hr/L

Cp t

mg.hr/L

AUMC

mg.hr2/L

AUMC

mg.hr2/L

3.23

0.25

1.96

0.649

0.649

0.49

0.0613

0.0613

0.5

1.44

0.425

1.07

0.72

0.151

0.213

0.75

1.22

0.333

1.41

0.915

0.204

0.417

1.12

1.12

0.254

0.671

1.25

1.07

1.97

1.34

0.307

0.978

1.5

1.03

0.263

2.24

1.55

0.982

0.503

2.74

1.96

2.22

0.82

1.8

4.54

3.28

5.24

7.46

0.686

1.51

6.05

4.12

7.4

14.9

0.525

1.82

7.86

4.73

13.3

28.1

12

0.402

1.39

9.25

4.82

14.3

42.4

24

0.137

3.23

12.5

3.29

48.7

91.1

Infinity

will prevent you getting credit for this problem

To get credit for this problem print this page, work the problem and

You will have one chance to submit your answers for this problem [# 3120802476]. You can try

the homework problem more than once with different data to improve your grade. Your highest

score is recorded. After submitting your answers you can use the browser back arrow to get back

here and see how the compuer worked the problem.

Some Equations:

Equation 30.4.2 AUC for the last segment from tlast to infinity

where k' is the slowest rate constant. k' can be calculated from the terminal slope of Cp versus

time on semi-log graph paper.

Equation 30.4.3 AUMC for the last segment from tlast to infinity

where k' is the slowest rate constant. k' can be calculated from the terminal slope of Cp versus

time on semi-log graph paper.

- Calculations used to determine patient-specific doses “The right dose”Uploaded byekrams
- CTD Guidance -FinalUploaded byPatel Prakashkumar
- Anvisa Ba-be GuidelinesUploaded bytaresh41
- B. Pharm.-ivth Year Syllabus (3)Uploaded bySaurav Ghoshal
- HarvoniUploaded bycalamus300
- Effect of Food on Pharmacokinetics of Meloxicam_ijsit_2.3.7Uploaded byInternational Journal of Science Inventions Today
- 1997 PharmacolRev 49 403 LinUploaded byWayne Anderson
- Oxindoles and Their Pharmaceutical Significance- an OverviewUploaded byRudrangispharmacy
- art04Uploaded byJohn Alex
- Quantifying CA AbsorbtionUploaded byHera Dwi P
- Comite de Expertos LME OMS 2015Uploaded byJose Angel Mg
- clinical_chemistry_at_ummc_and_vamc.pdfUploaded byAnu Anusha
- 156-288-2-PBUploaded byJeje JeLovje
- The Sex Influence on PharmacokineticUploaded byIuliaC
- IVT Completion FormUploaded byJohn Henry Valencia
- Ibrucent 140 Capsule 90Uploaded byzaker hasan
- seminer.......BPUploaded byDipankar Das
- Dr Ankit's Complete List of Drugs and Consumables for Liver Transplant CaseUploaded byAnkit Sharma
- 13Uploaded byrezthu
- life or deathUploaded byapi-466404489
- Retigabine|cas 150812-12-7|サプライヤー 購入Uploaded byDC Chemicals
- 1-s2.0-S1319016413001114-mainUploaded byEr Omkar Ravindra Mhatre
- listUploaded byTheresa Carter
- Immunization ScheduleUploaded byAndre R. Reynolds Anglin
- CLONIDINE HYDROCHLORIDEUploaded bybluetonks
- 1-s2.0-S2213219818300898-mainUploaded byelevenia_email
- ftp chart1Uploaded byapi-286531621
- AsmaUploaded byMel Da
- Case Presentation Station 3B Drug Study ClinidineUploaded byRoey Rubian
- 2014-01-22-PLLRUploaded byYunan Syahban Maskat

- Dev Kota 2007Uploaded bysedalatianz
- Cert of FinancesUploaded byIris Le
- Topical and Transdermal Drug Products—Product Quality Tests.pdfUploaded bysedalatianz
- fda ruleUploaded bysedalatianz
- Power of Self-controlUploaded byRadu Dascalescu
- 61_585Uploaded bysedalatianz
- Biochemistry Research International 854687Uploaded bysedalatianz
- V19N07_409Uploaded bysedalatianz
- elias barreiro-guitar music of cuba.pdfUploaded bysedalatianz
- pnf018-04-05Uploaded bysedalatianz
- PHAR 7632 Chapter 25 Clinical ApplicationsUploaded bysedalatianz
- Analysis of Urine DataUploaded bysedalatianz
- Oxyresveratrol as the Potent Inhibitor on Dopa OxidaseActivity of Mushroom TyrosinaseUploaded bysedalatianz
- resveratrol botanical origin.pdfUploaded bysedalatianz
- Whitening and Antierythemic Effect of a Cream ContainiUploaded bysedalatianz
- Two Flavonoids From the Leavs of Morus AlbaUploaded bysedalatianz
- Exploring the potential of using algae in cosmetics 2015.pdfUploaded bysedalatianz
- Curcuma sumiyoshi2009Uploaded bysedalatianz
- Singing NoteUploaded bysedalatianz
- my lyricsUploaded bysedalatianz
- This is Your Brain on MusicUploaded bysedalatianz
- Westside-for-Skinny-Bastards-by-Joe-DefrancoUploaded byJason Clusiault
- prelipinsUploaded byReed Tompkins
- Toxic SubstancesUploaded bysedalatianz
- Gas Poisoning WordUploaded bysedalatianz
- !BudgetUploaded bysedalatianz
- Fpgec Application Bulletin 0214cUploaded bysedalatianz
- IdlUploaded bysedalatianz
- Khata NoskhehUploaded bysedalatianz

- Marina MihaljeviC. Change in Byzantine ArchitectureUploaded byNikoloz Nikolozishvili
- Temozolomide drug mannualUploaded bygubdia
- aci06-materials.pdfUploaded byAisha
- Pam 8002Uploaded byPedro Torres Heredia
- The Invention and Reinvention of Japanese CultureUploaded bySilvia Pelegrí
- test prepUploaded byIrfan Zargar
- Chapter 2 Road Planning and ReconnaissanceUploaded byqatarstructz30
- Rotational viscometers and typesUploaded byanur33
- Autoclave Validation MSPDAUploaded byYessine Mrabet
- steel makingUploaded bys.sam
- Aerodynamic Design and Optimization of a Long Rang UavUploaded byAhmed Hassan
- EOC5611P_UserManual_v1.0_20100328Uploaded byDavid Pimentel
- Details Information About Port NyanzaruUploaded byItai Assaf Raizman-Greif
- Different FablesUploaded byFlorence Requilman
- Hariti Temple of SwayambhuUploaded byMin Bahadur shakya
- Chapter 8.pdfUploaded byJonathan Aylas
- DRUN LEVEL CONTROL.pptxUploaded byAshvani Shukla
- Summa Theologica - Q90-97Uploaded bySky Ng
- Rosuvastatin Induced Rhabdomyolysis in a Low Risk PatientUploaded bydear5643
- Catalogo de compresores BristolUploaded bysalvatore
- Introduction to Operation Management.pptUploaded bySwati Kataria
- I Have Lived BeforeUploaded byyogana
- 7 Mistakes Everyone Makes When They Upgrade to LEDsUploaded bykathlitesaverscomau
- Base Plate Uc152x152x23Uploaded bysonofalexander
- University of South Carolina Game Traffic 2010Uploaded byThe State Newspaper
- BEAMS_Unit 3 Algebraic Expressions and Algebraic FormulaeUploaded byrea0079
- Discussion of RustingUploaded byShamil Azha Ibrahim
- NPN TransistorUploaded bysphinx
- NEW Sub Module 11.4 Air Conditioning and Cabin PressurisatioUploaded byAhsan Malik
- DeforestationUploaded bythangave2000