Test

• Undergraduate– 24 Questions: Multiple Choice, Fill-in and T/F– 3 Problems

• MS– 3 Questions: Multiple Choice, Fill-in and T/F– MS grade: Undergrad Part * 0.9 + MS Part

• Check out the point number per question.– Not all questions are created equally.

Tips for working out problems

1. (30%) Write out the equations. Be sure to use the correct symbols from the book or my lectures.

Do not put unnecessary equations in.2. (40%) Show all your work. Each step.3. (20%) Correct answer4. (10%) Correct units with the answer

EXTRAVASCULAR DOSE KINETICSLecture #13

Extravascular Routes of Administration

• Enteral (GI Tract)– oral, sub-lingual, buccal, rectal

• Parenteral (injection/infusion)– Not IV or IA– IM, SC, ID

• Skin (Patch)• Lungs

– Inhalation• Vaginal (local)• Eye (local)

X

Oral Dosage Forms

• Immediate release• Modified release– Extended Release– Delayed Release– Targeted Release– Oral disintegrating tablets (ODT)

Drug

Abs

orbe

dDr

ug A

bsor

bed

Drug

Abs

orbe

d

Time

Time

Time

A

B

C

Kinetics of Absorption

Liver

GI Tract

AortaVena Cava

HepaticArteryHepatic

Vein

HepaticPortalVein

HepaticPortalVein

Gall Bladder

BileDuct

Heart

skinfat

ka

Absorption Kinetics: First Versus ZeroFr

actio

n Dr

ug R

emai

ning

in th

e GI

Tra

ct

Not Concentration Dependent

Concentration Dependent

Absorption Kinetics: First Versus ZeroFr

actio

n Dr

ug R

emai

ning

in th

e GI

Tra

ct

Cartesian Plot Semilogarithmic Plot

Absorption Kinetics without EliminationGI Tract Blood Plasma

1st Order

Zero Order

First Order Absorption Kinetics

Half-time of Absorption

Absorption Rate Constant

Amount being Absorbed

First Order Absorption Kinetics with Elimination

1st Order

Absorption Kinetics with EliminationGI Tract Blood Plasma

1st Order

Zero Order

EliminationPhase

EliminationPhase

Absorption Phase

Absorption Phase

Oral vs IV

IV

Oral

“Intestines”

“Blood Plasma”

“Liver”

Bioavailability (F)

• Fraction of the oral dose systemic circulation

AUC = Area under the Curve ((mg*hr)/L)F = BioavailabilityAdose= Dose (mg)CL=Clearance (L/hr)

Increasing Dose

AUC?Cmax?Tmax?ka?k?

Dose (A) AUC CMAX tmax ka k

increase increase increase no effect no effect no effect

decrease

decrease

decrease

no effect no effect no effect

Absorption vs. Elimination

Blood Plasma

Abso

rptio

n

Elim

inati

on

Absorption vs. Elimination

Blood PlasmaAbsorptionElimination

AbsorptionElimination

Blood Plasma

Elimination Rate Limiting

Absorption Rate Limiting

Confusing thing in the Book: Disposition Limited, when disposition refers to ADME according to several references.

Elimination is “Rate” LimitingAbsorption >> Elimination Absorption > Elimination

Cmax

Cmax

AUC=0.42 (mg*hr)/L AUC=0.32 (mg*hr)/L

AUC (IV) = 0.48 (mg*hr)/L

ka=0.7 /hrk=0.1 /hr

ka=0.2 /hrk=0.1 /hr

Absorption is “Rate” Limiting

ka=0.05 /hrk=0.1 /hr

Absorption < Elimination

AUC=0.16 (mg*hr)/L

AUC (IV)=0.48 (mg*hr)/L

Cmax Cmax

Absorption = Elimination

ka=0.1 /hrk=0.1 /hr

AUC=0.24 (mg*hr)/L

Absorption Phase?

Distinguishing effects on absorption and elimination

• Strategies– Different Dosage Forms– Different Routes

Absorption vs. Elimination

chronic obstructive pulmonary disease (COPD)asthma

*Similar compounds in Chocolate

500 ml water in Empty Stomach

20 ml water in Empty Stomach

20 ml water in Full Stomach

Absorption vs. Elimination

oil

oil + aluminum monostearate

aqueous

Distinguishing between absorption and elimination rate limitations

Increasing ka

Increasing ka

Increasing k

Increasing k

Elimination rate constant (k) is constant Absorption rate constant (ka) is constant