Download PHAR 750 Syllabus 2015

OSU/OHSU COLLEGE OF PHARMACY
Mission Statement
The College of Pharmacy is dedicated to fostering graduates and professionals who will maximize the
health of the public by advancing patient care and facilitating the discovery, understanding, and cost
effective use of medicines.
Course Syllabus: PHAR 750
Fall 2015 Pharmacokinetics/Biopharmaceutics
Faculty:
J. Mark Christensen, PhD, R.Ph.
Contact Information: [email protected]
I.
General Catalog Description
PHAR750 Pharmacokinetics/Biopharmaceutics, 4 credits. Pharmacokinetics and
bioavailability of drugs in clinical care, including changing disease states. Approved for
use on a graduate program of study. This course meets for two hours twice per week.
PREREQS: PHAR 734, PHAR 735 or graduate standing in Pharmaceutical Sciences.
COREQ: PHAR 752
II.
General Goal
-
III.
Have the ability to appropriately calculate pharmacokinetic parameters for drugs
administered via the intravascular and extravascular routes using data from various
methods of measuring clinical effectiveness.
Describe and calculate the disposition characteristics of drugs through various body
compartments using kinetic methods.
Develop the ability to evaluate factors influencing the drug availability that impact
effectiveness in drug treatments.
Given a patient situation and characteristics of the drug to be used in that patient’s
treatment, the student should be able to recommend a particular route of administration
and potential formulation for the recommended product.
Outcomes and Objectives
SPECIFIC COURSE OBJECTIVES
1. Define the basic pharmacokinetic parameters of a drug: volume of distribution, clearance terms,
extraction ratio, elimination half-life, unbound fraction and to understand how these parameters are
related. Define and differentiate between rate and rate constant.
2. Describe processes that underlie absorption, distribution, metabolism, and elimination of drugs in
the body including the role of compartment models in determining time course of blood levels.
3. Describe, define and determine the pharmacokinetic parameters of a drug using plasma
concentration or urinary excretion data.
4. Describe and be able to quantify the pharmacokinetics of per orally (p.o.) administered solid
dosage forms, multiple dosing, intravenous administration with and without a loading dose, and
constant rate infusion.
5. Demonstrate how the first pass effects (upon oral administration) can be predicted.
6. Utilize appropriate pharmacokinetic parameters and principles to solve and/or explain drug
therapy problems.
7. Determine/calculate the appropriate pharmacokinetic parameters that mathematically describe drug
disposition in the body, including absolute and relative bioavailability.
8. Develop a dosage regimen from knowledge of the pharmacokinetics and therapeutic window of a
drug that also include the patient-specific or population (average) pharmacokinetic data.
9. Design optimal drug dosing based on knowledge of individual patient characteristics, availability of
dosage forms, utilizing appropriate monitoring procedures, and consideration of adherence issues.
PERFORMANCE OBJECTIVES:
1. To calculate pharmacokinetic parameters given sets of timed plasma concentrations
after various routes of administration.
2. Given pharmacokinetic equations, to construct plots which demonstrate (i) the
dependence of various pharmacokinetic parameters on dose of drug and (ii) the
interdependence between parameters.
3. Given a table of pharmacokinetic parameters: (i) to calculate a dosing regimen; (ii) to
predict extent of first pass effect (bioavailability).
IV.
Course Content
Review Compartmental Pharmacokinetic analysis (2.0 hrs.)
- IV and Oral equations for Clearance, Volume of Distribution, half-life, AUC, Ka and K.
- Equations for IBW, AdjuBW, and Creatinine Clearance
Two-Compartment Model: (4.0 hrs.)
- Elimination Half-life, Volumes of distribution, First-order elimination, excretion rate
- Models equations for A, B, α, β, AUC, Cl, Half-life, Vc, Varea and F.
- Equations for fraction of the dose remaining, total clearance, clearance, renal clearance,
- Method of residuals, Lidocaine example for clinical kinetics
Extravascular Drug Administration: (5 hrs.)
- First- and zero-order absorption, bioavailability, extent of absorption, first-pass effect
- determining absorption, disposition alteration of rate of absorption, area under the curve,
clearance, volume of distribution, plasma concentration, and amount of drug in body
- Half-life, absorption rate constant, method of residuals, stripping data.
- Valproate example for clinical kinetics
Implications of altered Plasma protein binding and pharmacokinetics (2.0 hrs. lecture)
- Models describing Protein binding and drug tissue distribution
- Saturation of protein binding.
Noncompartmental Pharmacokinetic Analysis (3.0 hrs.)
- Processes to calculate Areas Under the plasma Concentration time curve.
- Trapezoidal rule and it power and short comings.
- Area under First and Second Moment drug Concentration time Curves.
- Calculation of Pharmacokinetic Parameters using Statistical Moment theory.
- Mean Resident Time, Vss, Clearance, Cave, and Dosing intervals.
Nonlinear Pharmacokinetics (3.0 hrs.)
- Michaelis-Menten Kinetics
- Lack of drug concentration and AUC proportionality versus dose.
- Mullins (Eadie-Hofstee) plots for Vm and Km.
- Principles of dosing drugs following Non-linear Pharmacokinetics
Phenytoin Clinical Pharmacokinetics (4.0 hrs.)
- Dosage Forms of phenytoin and FosPhenytoin.
- Pharmacokinetic parameters
- Metric method to calculate loading dose and maintenance doses (examples).
- Nomograms for Phenytoin dosing
Drug Absorption (4.0 hrs. lectures)
- Review Anatomy and Physiology of the gastro-intestinal tract,
- Gastric emptying time, migrating myoelectric complex, GI transit,
- Effect of food on gastric emptying and bioavailability
- Transport systems of the GI tract (Passive, Active, Facilitative, P-glycoprotein)
- Other known Transporters in the GI, obstacles etc.
- Absorption windows, site for absorption of diuretics, antibiotics, iron.
- First pass effect, Drug Metabolism liver and in the GI tract
- Diseases affecting GI absorption
- Nonlinear Processes for drug absorption
- Effects of cardiac disease on blood flow, drug distribution, clearance, and absorption
- Particle size, drug crystal structure effects on rate and extent of drug absorption
Bioavailability (3 hrs. lecture)
- Bioavailability definitions,
- Use of AUC, Cmax, Tmax, for bioequivalence and examples
- Urinary data, blood data, dissolution data and examples for bioavailability
- BCS/MCS classification for bioavailability
- In-vitro in-vivo correlations
- USP approved drug products and legal requirements for drug substitution
- Effects of humidity and product storage on bioavailability
Renal Drug Excretion (3 hrs. Lecture)
- Renal excretion as a fraction of total elimination, urinary excretion rate data
- Renal Failure and drug excretion
- Drug nomograms used for dosing renally excreted drugs
- Disease states and renal drug excretion
- Effect of urinary pH on bioavailability
- Modification of urinary pH and its effects on drug excretion
Drug Metabolism (4 hrs. lecture)
- Short Review Liver and drug metabolic processes, hepatic enzyme induction
- Hepatic extraction ratio, E, first pass effect and predictive calculations
- Drug excretion into the bile
- Liver disease and drug excretion
- Effects of food on drug metabolism
- Enantiomeric drug metabolism
- Gender differences in drug metabolism
- Age (infants and elderly) effects on drug absorption, disposition and metabolism
V.
Student Requirements for Credit and Evaluation of Performance
Grading:
First Midterm
Second Midterm
Third Midterm
Assignments
Total Points
100 points
100 points
100 points
100 points
400 points
A=
B=
C=
D=
F=
≥ 90%
80% - 89%
70% - 79%
65% – 69%
< 65%
A curve may be used in assigning grades in this class at the discretion of the Course
Coordinators. No test scores are "dropped" and no "re-takes" will be offered for poor
performance.
VI.
Learning Resources
Professors of the course and GTA and textbooks, Concepts in Clinical PK, 5th Edition, by Am. Soc.
Health-System Pharmacists and Applied Clinical Pharmacokinetics, Bauer, 2nd Edition
VII.
Faculty Members Responsible for Course
Dr. J. Mark Christensen PhD, RPh
VIII. Statement regarding students with disabilities
The College of Pharmacy will work to accommodate student disabilities to maximize
opportunities for success. If a student suspects a disability may be limiting their performance it
is their responsibility to contact OSU’s Disability Access Services (DAS). Accommodations are
collaborative efforts between students, faculty and DAS. Students with accommodations
approved through DAS are responsible for contacting the faculty member in charge of the
course prior to or during the first week of the term to discuss accommodations. Students who
believe they are eligible for accommodations but who have not yet obtained approval through
DAS should contact DAS immediately at 541-737-4098.
IX.
Statement regarding Civility and Student Behavior
The goal of Oregon State University is to provide students with the knowledge, skill and wisdom
they need to contribute to society. Our rules are formulated to guarantee each student’s
freedom to learn and to protect the fundamental rights of others. People must treat each other
with dignity and respect in order for scholarship to thrive. Behaviors that are disruptive to
teaching and learning will not be tolerated, and will be referred to the Student Conduct Program
for disciplinary action. Behaviors that create a hostile, offensive or intimidating environment
based on gender, race, ethnicity, color, religion, age, disability, marital status or sexual
orientation will be referred to the Affirmative Action Office. Please reference the University’s
mission and values statement.
X.
Statement regarding Academic and Professional Standards
The Oregon State University Student Conduct Regulations define several expectations of
students (http://oregonstate.edu/studentconduct/offenses-0)
The College of Pharmacy professional program has defined additional academic and behavioral
expectations and characteristics considered essential to being a student pharmacist and
pharmacist. Individuals who choose to become student pharmacists do so with the
understanding that admission, progression and graduation are dependent upon their capacity to
personally demonstrate essential characteristics defined by the College and profession of
pharmacy
(http://pharmacy.oregonstate.edu/files/ctools/essential_characteristics_of_student_pharmacists.pdf ).
Ethical standards in the College of Pharmacy require both a personal commitment to honesty
and a commitment not to tolerate dishonesty in others. The penalty for breaches of
acceptable conduct such as cheating, plagiarism or tolerating similar conduct in other
students is a grade of “F” for the assignment/paper and for the course. More severe
penalties may be assigned after consultation with the College Academic Professional Standards
(APS) Committee and may result in dismissal from the College of Pharmacy. Students are
encouraged to ask course instructors, refer to the pharmacy student handbook and examine
university academic regulations if there are any questions regarding acceptable behavior. More
detailed information may be found at: http://oregonstate.edu/studentconduct/offenses-0
XI.
Evaluation and Improvement of Course Quality
Students have several opportunities to participate in continual quality improvement of
courses. The College of Pharmacy utilizes standard evaluation tools developed by the
university and facilitates periodic student review of the curriculum. The College of
Pharmacy Curriculum and Assessment committees have student committee members
and students are encouraged to bring suggestions for improvement directly to members
of these committees.
XII.
Testing Policy
All quizzes and tests will be administered at the regularly scheduled class time in course
class room unless otherwise announced in class.
Students must arrive on time for quizzes and examinations. All instructions and
corrections will be made at the beginning of the examination period and will not be
repeated. Students arriving after a quiz/test has been handed in by another student will
not be allowed to sit for the examination and may receive a score of zero for the exam.
Absences on quiz or test days must be approved by the Course Coordinator prior to the
scheduled test. Requests must be in written form and given to the Course Coordinator. If
permission is granted by telephone at the last minute (e.g. due to illness, accidents, etc),
it is the student's responsibility to confirm the request in writing as soon as possible. If
permission is given to miss any of the midterms, the weighting of the following midterms
or the comprehensive portion of the final third midterm will be increased proportionally. No
make-up test or quiz will be given for any reason for any of the exams/quizzes scheduled
during the course. An unexcused absence from a test or quiz may result in a grade of "0"
for that test or quiz. This is the established procedure for a missed test/quiz. Please do
not request a "special" exception such as taking a test or a quiz either early or late unless
the request is made during the first week of the term.
Assignments must be turned in at the beginning of class of the day that it is due.
Assignments that are turned in late will have points deducted prior to grading.
All students must take the final midterm examination. A student entering the final midterm
examination with a grade of C or above who must miss the final midterm examination for
an approved reason will receive an incomplete for the course and must make up the final
midterm exam within one year at a regular scheduled final exam. A student who misses
the final exam without an approved excuse will receive a grade of F for the course.
Answers to multiple choice questions are based on the scan sheets and not answers
written on the test papers. All tests are taken to the Measurement and Evaluation
department for grading. After the tests have been graded and an item analysis has been
performed, questions may be discarded at the discretion of the Course Coordinator.
XIII.
Faculty and Course Evaluations
Faculty and course evaluations are an essential component of the College’s assessment
plan and the faculty promotion and tenure process. Student feedback is used to improve
instructional and curriculum quality.
Participation in faculty and course evaluations is a required component of all pharmacy
courses. In order to receive a grade for a course, students must log in to all required
faculty and course evaluations for that course. Emails from Nancy Baker will be sent to
all students in the course, providing the required log in information. Students will need to
enter their student ID number to transfer them to the faculty or course evaluation site.
Student ID numbers will NOT be linked to answers provided on faculty and course
evaluations. Students may opt out of completing individual faculty and course evaluations
once they have logged in with their student ID number.
Completed by:
Dr. J. Mark Christensen
09/14