1. 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.

2. 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

3. EXTRAVASCULAR DOSE KINETICS Lecture #13

4. 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

5. Oral Dosage Forms Immediate release Modified release – Extended Release – Delayed Release – Targeted Release – Oral disintegrating tablets (ODT) Drug Absorbed Time A B C

6. 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

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

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

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

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

11. First Order Absorption Kinetics with Elimination 1 st Order

12. Absorption Kinetics with Elimination GI Tract Blood Plasma 1 st Order Zero Order Elimination Phase Elimination Phase Absorption Phase Absorption Phase

13. Oral vs IV IV Oral

14. “Intestines” “Blood Plasma” “Liver”

15. 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)

16. 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

17. Absorption vs. Elimination Blood Plasma Absorption Elimination

18. 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.

19. 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

20. 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?

21. Distinguishing effects on absorption and elimination Strategies – Different Dosage Forms – Different Routes

22. 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

23. Absorption vs. Elimination oil oil + aluminum monostearate aqueous

24. 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