1. Kinetics Tutoring
Allie Punke

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

3. Obese patients Absorption Distribution Metabolism Excretion
More efficient nutrient absorption….
- Increased GI emptying time and small intestine transit time
Increased Vd for lipophilic drugs
Increased AAG1
- Decreased fup of basic drugs
Increased activity of CYP2E1
High extraction drugs = Dec CL
Phase I – not affected
Phase II – may be increased
Increased

4. Geriatric Patients Absorption Distribution Metabolism Excretion
Less acid, increased gastric pH
TBW: less
Fat : Increased
Albumin: Decreased
AAG1: Increased
Decreased hepatic CL
Phase I – affected more so
Phase II
Decreased

5. Pregnant Patients Absorption Distribution Metabolism Excretion
pH: increased gastric pH
Decreased Gastric emptying and small intestine motility
Increased
Increased Vd for hydrophilic drugs , increased fat = Inc Vd for lipophilic drug
Albumin- not affected much
AAG1: Increased
Increased metabolic activity of : 3A4, 2C9, 2D6, 2D9
Decreased metabolic activity: 2C19, 1A2

6. Pediatric patients Absorption Distribution Metabolism Excretion
pH: Increased
Surface area: decreased
Motility: decreased (neonates), increased (infants)
Permeability: better
Muscular blood flow: less neonates, better in infants
TBW: increased
Albumin/protein: decreased
Fat tissue: Decreased – EXCEPT: brain
Serum bilirubin: higher
1. High  Low
2. Low  High
3. No difference
Other pathways
Overall, metablic rate decreased in neonates, starts increasing infants, children ~ adult values
Decreased
Protein: higher levels

7. Drug A has recently come to a RCT
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
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 2nd trimester
B. 86 year old female
C. 13 year old male
D. Obese patient with BMI > 30

10. A. pregnant woman in her 3rd trimester B. 86 year old female
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 3rd trimester
B. 86 year old female
C. 13 year old male
D. Obese patient
E. B and D
F. A and D
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 D

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
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 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. Bioequivalent or Not?
In the following bioequivalence studies, note whether the products would be considered to be bioequivalent or not
1.05 ( )
1.2 ( )
0.93 ( )

24. 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
1. BX
2. BC
3. B*
4. AB
5. A
6. B

25. You are a retail pharmacist and get a rx for Volunteerapril 23mg
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.
Volunteerapril
AB2
Tylerbrayon
AB1
Justinhunteride
Derickdooleyzide
Which medication do you dispense?
Tylerbrayon
Justinhunteride
Derickdooleyzide
Tell pt they have to wait for you to order it

26. You get another prescription for peytonide
You get another prescription for peytonide. You see from your manufacturer that it is on backorder. Which of the following can you order instead?
Broncomide BX
Peytonide
AB1
Steelernib
Manningolol
AB2
Broncomide
Stellernib
Manningolol
Call the MD

27. 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.

28. Questions?