PHAR 7632/7633 Syllabus

Topics to be Covered in PHAR 7632 and PHAR 7633

Glossary

1. Introduction (PHAR 7632) (Slides in PDF Format)
2. Mathematical Material
   • exponents and logarithms (Slides in PDF Format)
   • graphing data, linear and semi-log plots (Slides in PDF Format)
   • use of spreadsheets (Slides in PDF Format)
     [An example Spreadsheet - includes a macro so you may get a warning from Excel]
   • calculus, differentiation and integration (Slides in PDF Format)
     Textbook pp 49-51
   • integration using Laplace transforms
     [Table of Laplace Transforms in PDF format]
     [Spreadsheet Example for StepSize adjustment with Euler's Method]
     Textbook pp 41-49
     Useful References
     1. Mayersohn, M. and Gibaldi, M 1970 "Mathematical Methods in Pharmacokinetics. I. "Use of the Laplace Transform in Solving Differential Rate Equations," Amer. J. Pharm. Ed., 34:608-614
   • Area under the Cp versus Time Curve (AUC) and the Trapezoidal Rule (Slides in PDF Format)
     • One Compartment IV Bolus Stack with sample AUC calculations - HyperCard Stack
     • Some example data sets created with this stack
3. Pharmaceutical Analysis
   • spectroscopic drug analysis (Slides in PDF Format)
   • HPLC (Slides in PDF Format)
     Booklet pp 26-33
   • GLC (Slides in PDF Format)
     Booklet pp 19-22
   • RIA (Slides in PDF Format)
     Booklet pp 36-39
   • EMIT (Slides in PDF Format)
     Booklet pp 40-42
   • FPIA
     Booklet pp 42-43
   • Comparison of Methods
     Booklet pp 46-47
4. Pharmacokinetics introduction
5. One compartment IV bolus, Plasma data, Volume, AUC, Half-life (Slides in PDF Format)
   Textbook pp 19-22
6. Modeling
   • Why Model
     Textbook pp 1-8
   • General Method
     [Excel Spreadsheet for Parameter Adjustment]
     Textbook pp 9-19
7. More Laplace transforms
   Textbook pp 44-48
   Useful References
   1. Mayersohn, M. and Gibaldi, M 1971 "Mathematical Methods in Pharmacokinetics. II. "Solution of the Two Compartment Open Model," Amer. J. Pharm. Ed., 35:19-28
   2. Benet, L.Z. and Turi, J.S. 1971 "Use of the General Partial Fraction Theorem for Obtaining Inverse Laplace Transforms in Pharmacokinetic Analysis," J. Pharm. Sci., 60:1593-1594
   3. Benet, L.Z. 1972 "General Treatment of Linear Mammillary Models with Elimination from any Compartment as Used in Pharmacokinetics," J. Pharm. Sci., 61:536-541
8. Program set-up
   • Boomer (Boomer On-line Manual - Chapter Four and Boomer On-line Manual - Chapter Six)
     1. Multi IV Bolus Dose Simulation - Two Compartment (27 Jul 99)
     2. Simultaneous fit to IV and Oral Data - Two Compartment IV Bolus (IV and Oral Data files)
   • SAAM II
     SAAM II Manual (On reserve in the Bird Library)
     Notes re the use of SAAM II
     1. Comparison between SAAM II and Boomer Weighting Schemes
     2. Fitting Multiple Lines with SAAM (Plasma and Urine)
     3. Fitting Plasma and Heart Rate Data with SAAM II
   • WinNONLIN Professional
     WinNONLIN Manuals (On reserve in the Bird Library)
   • ADAPT II Release 4
     The ADAPT II manual can be downloaded as a PDF file
     ADAPT II can be run from Binger on the OUHSC Campus if you have account on this machine.
9. Program Output Evaluation (Slides in PDF Format)
   Boomer and SAAM II control/example files,
   Textbook Chapter 8, pp 95-110
10. Numerical Integration (Slides in PDF Format)
    [Spreadsheet Example for StepSize adjustment with Euler's Method]
    Textbook pp 49-55
11. Optimization (Slides in PDF Format)
    Textbook pp 75-82
12. Analysis of Urine data, plot types, clearance, metabolism, renal function (Slides in PDF Format)
13. Weighting Schemes, Fitting data sets simultaneously (Slides in PDF Format)
    [Spreadsheet Example for Determining 'a' and 'b' (NOTE: this file uses a Macro)]
    [A Two data sets .BAT file (Ch9905b.BAT) with the required data sets (Ch9905bp.DAT and Ch9905bu.DAT). One output files was Ch9905.OUT]
    Textbook pp 83-88

    PHAR 7633

14. Introduction (PHAR 7633)
15. Intravenous infusion, Steady state concentration, slow-fast infusion, post infusion (*)
    IV - Infusion (Boomer BAT file)
    IV - Infusion (Setting up the Problem using SAAM II)
16. Routes of drug administration (*)
17. Pharmacokinetics of oral administration (*)
    Oral Dose Simulation (Boomer .BAT file)
    Oral Dose Simulation (SAAM Data file) [This is a SAAM data file. You will need to de-binhex the file and then open it after opening SAAM II. Ask if you need the ancient Druid incantation for the de-binhexing...or try downloading Expander or Unstuff available on the Aladdin Systems web-site]
18. Bioavailability calculations, Method of residuals, W-N method (*)
    Oral Dose Fit to Method of Residual Data (Boomer .BAT file)
    Oral Dose Fit to Method of Residual Data (SAAM Data file)
    Oral and IV Dose Fit to Method of Residual Data (Boomer .BAT file)
    Oral and IV Dose Fit to Method of Residual Data (SAAM Data file)
19. Selection of the "best" Model
    Textbook pp 95-110
20. Identifiability
    Textbook 114-120
21. Bioavailability studies, statistics (*)
    On-line Resources
    • Food and Drug Administration (FDA)
      • FDA Enforcement Report Index
      • Center for Drug Evaluation and Research, FDA
      • Federal Register Documents related to FDA
      • Search the FDA Web site
22. Physiological factors affecting oral absorption (*)
23. Physical-Chemical factors affecting oral absorption (*)
    • Brodie D Value Stack - HyperCard Stack
24. Formulation factors affecting oral absorption (*)
    • Disintegration Testing - HyperCard Stack
25. Multiple Bolus IV dose administration (*)
    • tau And Dose calculation - Practice Problems
    • Cpmin/Cpmax calculation - Practice Problems
26. Multiple Oral Dose Administration (*)
    • Approximation for Three Equations - Excel Spreadsheet
    • Superposition of IV Bolus Doses - Excel Spreadsheet
    • Superposition of Oral Doses - Excel Spreadsheet
27. Routes of excretion (*)
    • Cp Average Calculator On-line Javascript Calculator
    • Cpmax/Cpmin Calculator On-line Javascript Calculator
28. Metabolism (*)
29. Drug distribution (*)
30. Multi-compartmental pharmacokinetic models (*)
    • Practice problems - Using the method of residuals
    • Practice problems - Non compartental calculations
31. Non-linear pharmacokinetic models (*)
    • Practice problems - Calculating a suitable dosing regimen
32. Clinical Applications of Pharmacokinetics (*)
33. Optimal sampling
    Textbook pp123-129
34. Bayesian Analysis and Population modeling
    Textbook pp 88-94
35. Pharmacodynamic models
36. Saturable Protein Binding, Physiologically based pharmacokinetic models

• Textbook == Mathematical Modeling of Pharmacokinetic Data by David W.A. Bourne
• Boomer == Boomer On-line Manual
• Booklet == Pieper, J.A. and Rutledge, D.R. 1989 Current Concepts - Laboratory Techniques for Pharmacists, Upjohn, Kalamazoo, MI (Upjohn Publication #8804-03 June 1989) (On reserve in the Bird Library)
• (*) Links to relevant or similar material from PHAR 4634 Online