1. Kinetics Tutoring ALLIE PUNKE

2. Special Populations Elderly/Geriatrics Pediatrics Obesity Pregnancy ADME! ◦Look at the differences ◦Recommend making a chart that shows up/down for different parameters

3. Obese patients AbsorptionDistributionMetabolismExcretion

4. Geriatric Patients AbsorptionDistributionMetabolismExcretion

5. Pregnant Patients AbsorptionDistributionMetabolismExcretion

6. Pediatric patients AbsorptionDistributionMetabolismExcretion

7. Drug A has recently come to a RCT. It has been shown that it exhibits a high lipophilicity. Which population would be least likely to need an adjustment of dose in this drug relative to the other populations? A. A woman in her third trimester of pregnancy B. A 9 year old child C. A morbidly obese male patient with BMI > 30 D. A 94 year old frail elderly woman

8. Additional studies on drug A have shown that it is useful for seizures. With this knowledge, which population is most vulnerable to accumulation of the drug? A. A 2 week old infant who recently experienced a febrile seizure B. A 9 year old child who recently experienced a febrile seizure C. An obese patient (BMI=32) D. A pregnant patient in her first trimester who has had epilepsy for over 10 years

9. The elimination of Drug B has been determined to be through a completely renal mechanism. Which patient would need a lower dose of medication relative to the others? A. pregnant woman in her 2 nd trimester B. 86 year old female C. 13 year old male D. Obese patient with BMI > 30

10. The elimination of Drug B has been determined to be through a completely renal mechanism. Which patient(s) would likely need a higher dose of medication relative to the others? A. pregnant woman in her 3 rd trimester B. 86 year old female C. 13 year old male D. Obese patient with BMI > 30 E. B and D F. A and D

11. A new cancer drug for AML, Sprycel (dasatinib), requires an acidic environment for absorption to occur. Which patient would likely have lower levels of absorption and thus less efficacy with this drug? A. 2 week old neonate B. 74 year old female C. 30 year old obese patient D. 29 year old pregnant patient E. A and D F. A, B, and C

12. Which population would exhibit increased volume of distribution for a new drug that is in the same class as the aminoglycosides, which are hydrophilic? A. A 87 year old man B. Morbidly obese woman (BMI=50) C. A newborn baby D. A 14 year old

13. Bioavailability + Equivalence

14. Bioavailability Rate and extent to which an active ingredient is absorbed from a drug product and becomes available at the site of action ◦Typically monitored in plasma and/or urine Factors that affect BA ◦Ka – rate of absorption ◦F – extent of absorption ◦CL – rate of elimination ◦Vd – rate/extent of absorption

15. Types of Bioavailability Absolute ◦The reference drug is always being given _________ ◦F is always Comparative (Relative) ◦Compares two drugs in different dosage forms ◦F is:

16. Bioequivalence Comparable bioavailability in any individual when administered in equivalent dosage regimen ◦Looks at:

17. Pharmaceutical Alternatives Contain the same: But differ in:

18. Therapeutically Equivalent Safe + effective Identical amounts of same active drug in same dosage form and route NOTE ◦If therapeutically equivalent, then it will be _______________ and ___________________

20. Mr. James is bad at remembering to take his medication. He has seen a commercial on television for Metoprolol XL. He wants to know if you can give him this medication instead of his metoprolol 50mg BID that his physician wrote for last month. A. Yes, these drugs are bioequivalent. B. Yes, these drugs are pharmaceutically equivalent. C. No, these drugs are pharmaceutical alternatives but not pharmaceutically equivalent. D. No, these drugs are pharmaceutical alternatives but are not therapeutically equivalent.

21. Which set of items is pharmaceutically equivalent? A. 25mg promethazine suppository; 25mg promethazine tablet B. 4 tablets of 75mg clopidogrel; 1 tablet of 300mg clopidogrel C. Both are pharmaceutically equivalent D. Neither are pharmaceutically equivalent

22. Bioavailability Calculate F: ◦The ER is 0.8, 76% is absorbed ◦How much (mg) will reach the bloodstream if the drug is formulated into 500 mg tablets and the patient takes two daily After 7 half-lives, about ____% (actually _____ %)of drug will be eliminated in the urine allowing bioavailability to be estimated ◦If 500 mg is given daily, how much drug would be expected to be in the urine at this time? ◦What about after 5 half-lives?

23. Calculations Calculate the absolute bioavailability. ◦IV : 750 mg, CL=25L/h ◦Oral: 70% escapes first pass metabolism, 50% absorbed from the gut, Dose=1000 mg, CL=30 L/h

24. Calculations Formulation 1: CL=40 ml/minute, 80% escapes first pass metabolism, 30% is absorbed, D=40 mg. Formulation 2: CL=25 ml/minute, 25% is not metabolized by first pass, 40% is absorbed, D=55 mg. ◦What is the relative bioavailability of the formulation 2 compared to formulation 1?

25. Bioequivalent or Not? In the following bioequivalence studies, note whether the products would be considered to be bioequivalent or not ◦1.05 (0.78-1.2) ◦1.2 (0.81-1.28) ◦0.93 (0.8-1.24)

26. Know the FDA Codes! 1. BX 2. BC 3. B* 4. AB 5. A 6. B ◦Cardizem CD (capsule extended release) and Diltiazem Extended Release (capsule extended release) for which no data has been submitted about bioequivalence ◦No known problems with bioavailability ◦Cardizem CD & Diltiazem Extended Release bioequivalence has been resolved and are now considered therapeutic equivalents ◦Two forms of Bupropion extended release for which data has been reviewed and the application is not extensive enough to determine bioavailability ◦New study determines that two forms of Trazodone that were therapeutically equivalent may actually not be. More studies need to be conducted. ◦Two drugs that are not bioequivalent

27. You are a retail pharmacist and get a rx for Volunteerapril 23mg. You do not currently have this drug in stock. You pull out your orange book to see if you have something you can substitute with. This is what you see. VolunteeraprilAB2 TylerbrayonAB1 JustinhunterideAB1 DerickdooleyzideAB2 Which medication do you dispense? A.Tylerbrayon B.Justinhunteride C.Derickdooleyzide D.Tell pt they have to wait for you to order it

28. You get another prescription for peytonide. You see from your manufacturer that it is on backorder. Which of the following can you order instead? BroncomideBX PeytonideAB1 SteelernibBX ManningololAB2 A.Broncomide B.Stellernib C.Manningolol D.Call the MD

29. Helpful Hints Look over Dr. Loveless’s practice questions –this is her testing style so it could behoove you to do so. Stuff for special populations – learn main differences as well as anything he stressed in class. Really understand the differences between bioequivalence, pharmaceutical equivalent, etc. Number of ½ lives required for urine washout studies Know the differences with the special populations.

30. Questions?