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 * 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 answer 4.(10%) Correct units with the answer

EXTRAVASCULAR DOSE KINETICS Lecture #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 Absorbed Time A B C

Kinetics of Absorption Liver GI Tract Aorta Vena Cava Hepatic Artery Hepatic Vein Hepatic Portal Vein Hepatic Portal Vein Gall Bladder Bile Duct Heart skin fat kaka

Absorption Kinetics: First Versus Zero Fraction Drug Remaining in the GI Tract Not Concentration Dependent Concentration Dependent

Absorption Kinetics: First Versus Zero Fraction Drug Remaining in the GI Tract Cartesian Plot Semilogarithmic Plot

Absorption Kinetics without Elimination GI Tract Blood Plasma 1 st Order Zero Order

First Order Absorption Kinetics Half-time of Absorption Absorption Rate Constant Amount being Absorbed

First Order Absorption Kinetics with Elimination 1 st Order

Absorption Kinetics with Elimination GI Tract Blood Plasma 1 st Order Zero Order Elimination Phase Elimination Phase 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 = Bioavailability A dose = Dose (mg) CL=Clearance (L/hr)

Increasing Dose AUC? C max ? T max ? k a ? k? Dose (A)AUCC MAX t max kaka k increase no effect decreas e no effect

Absorption vs. Elimination Blood Plasma Absorption Elimination

Absorption vs. Elimination Blood Plasma Absorption Elimination Absorption Elimination 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” Limiting Absorption >> EliminationAbsorption > Elimination C max AUC=0.42 (mg*hr)/LAUC=0.32 (mg*hr)/L AUC (IV) = 0.48 (mg*hr)/L k a =0.7 /hr k=0.1 /hr k a =0.2 /hr k=0.1 /hr

Absorption is “Rate” Limiting k a =0.05 /hr k=0.1 /hr Absorption < Elimination AUC=0.16 (mg*hr)/L AUC (IV)=0.48 (mg*hr)/L C max Absorption = Elimination k a =0.1 /hr k=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 k a Increasing k Elimination rate constant (k) is constant Absorption rate constant (k a ) is constant