Post on 20-Jan-2018
description
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