Roseman University of Health Sciences College of Pharmacy

IPPE ASSIGNMENT COVER SHEET

Please complete this form when submitting your IPPE assignment. Assignment must be typed.

IPPE ASSIGNMENT NUMBER _________1.13 Students Name Bension Mirzakan

Date submitted ___________3/16/2012____________________________ Professor writing the assignment Dr. Dey

IPPE 1.13 Pharmacokinetics in Practice I 03/16/12 Student Instructions When you arrive on site, you should begin working on achieving the learning objectives set forth below. When both you and your preceptor are satisfied with your achievement of the learning objectives, your preceptor may assign you some pharmacy-related work to complete your 8-hour day. Following the session, please complete the assessment form provided, and return it to the Nevada College of Pharmacy by the deadline indicated. Learning Objectives The student must demonstrate the ability to: 1. 2. 3. Summarize pharmacokinetic principles and information found in pharmacy related drug resources Identify and recognize the key concepts in Bioavailability and Bioequivalence. Identify and recognize the differences between total clearance, hepatic clearance and renal clearance.

Assignment

1. Assume that you have just made a new formulation of acetaminophen. Design
a protocol to compare your drug product against the acetaminophen drug products on the market. What criteria would you use for proof of bioequivalence for your new formulation?

Response: The protocols I would use as to test a new formulation of acetaminophen against the current acetaminophen drugs that are on the market are A. B. C. D. Bioavailability Bioequivalence Pharmaceutical and Therapeutic Equivalents Generic Substitutions.

To prove bioequivalence of the new formulation, I would measure the statistical differences within a given sample population and see if the differences are statistically significant when compared to the standards. Currently, the FDA guidelines states that bioavailability (the rate and extent of drug absorption) cannot differ in a range more than -20%/+25% with a p>0.05 confidence level. To confirm this, two one-sided statistical test (one to measure the bioavailability is not too low and the other testing the bioavailability is not too high).

2. Why does FDA require a food intervention study (food effect) for some generic drug products prior to approval? For which drug products are food effects studies required?

Response: The FDA requires a food intervention study for some generic drugs prior to approval because the test compares the same amount under fasting condition and conditions with a patient that a high fat breakfast. It shows the effects of food when the drug is administered. Food effect studies are required for drugs with modified release dosage forms and immediate release forms for which are suspected to change bioavailability with the presents of food. Some drugs that require a food interventions drugs are ibuprofen, naproxen, and MOAIs 3. How would you conduct a bioequivalence study for drugs that are not
systemically absorbed or for those drugs in which the Cpmax and AUC cannot be measured in the plasma? (Think, Think!)

Response: For drugs that are not systemically absorbed or drugs in which Cpmax and AUC cannot be measured in the plasma, I would conduct a urinary drug excretion bioequivalence study. After giving the patient a drug, it measures how much drug is excreted through the urine after a prolonged period of time. For each value you get, you add it until most of the drug is eliminated. This is not the preferred way since it does not easily give you a mean to determine what the peak values are and to calculate the time it takes to reach peak values. 4. Is clearance a better parameter to describe drug elimination than half-life?
Look up drug clearance (any one from your pharmacy) from its product insert. What is the difference between drug clearance and creatinine clearance?

Response: Both clearance and half-life are methods for which the liver uses to metabolize drugs. To determine which is better, it would have to depend on the type of drug being used/tested. Drugs that only affect a one compartment system (which include the heart, plasma, kidney, lungs, and liver), both half-life and clearance could be used for drug elimination. On the other hand, for drugs that affect a multi-compartment system (which includes an organ from the first-compartment system and another tissue), clearance would be a better parameter for drug elimination than half-life. Clearance is a direct measure of drug elimination regardless of the number of compartments, as long as the liver is a part of the central compartment. For example, Abilify has a clearance of -3.73296 (Vd 404L, t - 75h, ke - .693/75= 0.00924, Cl = Ke*Vd)

Drug clearance refers to a fixed volume of fluid (containing the drug) that is cleared of the drug per unit of time. Creatinine clearance refers to the rate of urinary excretion of serum creatinine.
5. Choose any two aminoglycoside antibiotics from your pharmacy and write the different dosage forms and strengths of these antibiotics.

Response: A. Tobramycin Comes in 0.3% solution (5mL) (For eye infections) and 40mg/mL (2mL) injection (for treatment of infections). B. Neomycin Comes in 500mg tables, Neosporin ointments (for infections), Neomycin with ploymxin 1% ophthalmic solutions, and suspension. 6. Why do you have extended interval dosing for some antibiotics? List some of
the antibiotics that are often given as extended interval dosing. Response:

We have extended interval dosing for some antibiotics because some antibiotics show post antibiotic effects, and the bacterial action of the antibiotics are concentration dependents, In addition, it has been proven just as effective and safer for patients to deliver medication in that way. It was designed to bactericidal activity by producing a higher peak concentration. Some antibiotics that work under extended interval dosing are tobramycin, gentamycin, and other antibiotics under the aminoglycoside class.