1. Valproic Acid Software and Presentation by: Ted, Rob, Jeff, Cassie, Tristan, Korin, Ron, Gabe, Matt, Judith, Lindsay

2. General Information Used in the management of multiple seizure types. Used in the management of multiple seizure types. Oral and IV forms Oral and IV forms Also indicated for management of bipolar affective disorder and possible migraine prevention. Also indicated for management of bipolar affective disorder and possible migraine prevention. Increases body’s production and response to GABA. Increases body’s production and response to GABA.

3. Therapeutic / Toxic Conc’s Cp ss range- 50 to 100 mcg/ml. Cp ss range- 50 to 100 mcg/ml. Upper limit of 175mcg/ml with proper monitoring. Upper limit of 175mcg/ml with proper monitoring. At concentrations >75 mcg/ml some patients may experience adverse effects. At concentrations >75 mcg/ml some patients may experience adverse effects.

4. Basic Clinical Pharmacokinetics Exhibits concentration dependant protein binding Exhibits concentration dependant protein binding Follows Non-Linear Kinetics Follows Non-Linear Kinetics Highly protein bound to albumin Highly protein bound to albumin Follows a basic 1-Compartment Model. Follows a basic 1-Compartment Model.

5. Clinical Implications Clearance is now dose or concentration dependant. Clearance is now dose or concentration dependant. Volume of Distribution is now affected by concentration-dependant plasma protein binding and its value should be 0.15 to 2.0 L/kg. Volume of Distribution is now affected by concentration-dependant plasma protein binding and its value should be 0.15 to 2.0 L/kg. Half Life 12 to 18 hrs for adults and is found by the eqn. t 1/2 =0.693xVd/Cl Half Life 12 to 18 hrs for adults and is found by the eqn. t 1/2 =0.693xVd/Cl

6. Software Structure Functional components of the software were segmented into “tiers” to make the application to support ease of use and maintainability Functional components of the software were segmented into “tiers” to make the application to support ease of use and maintainability Core Core Peripheral Peripheral Variable Variable Core

7. Core Components Contains foundational assumptions of the software Contains foundational assumptions of the software User Input requirements User Input requirements Kinetic Models Kinetic Models Changing the Core will cause global changes to functionality and require massive reworking of the system Changing the Core will cause global changes to functionality and require massive reworking of the system Intolerant to changes Intolerant to changes Core

8. Peripheral Components Contains slowly changing parameters Contains slowly changing parameters Changes cascade to most sections of the software Changes cascade to most sections of the software Changes tolerated, but should be rare and hidden from most users Changes tolerated, but should be rare and hidden from most users Provides extensibility of the application Provides extensibility of the application Includes reports charts, kinetic parameters Includes reports charts, kinetic parameters Core

9. Variable Components Continuously changing Continuously changing High tolerance to changes, incorrect / inappropriate input High tolerance to changes, incorrect / inappropriate input Patient Cases Patient Cases Core

10. Bayesian Pharmacokinetics Estimate drug dosage or steady state plasma concentration Estimate drug dosage or steady state plasma concentration Patient’s parameters (age, weight, sex, serum creatine) Patient’s parameters (age, weight, sex, serum creatine) Absence of or with measured drug levels Absence of or with measured drug levels DrugCalc shareware software DrugCalc shareware software Dr. Dennis Mungall Dr. Dennis Mungall Nonlinear regression Nonlinear regression One-compartment model One-compartment model

11. DrugCalc Example Enter patient’s demographic, drug dosing, and serum concentration Enter patient’s demographic, drug dosing, and serum concentration Compute the pharmacokinetic parameters Compute the pharmacokinetic parameters Compute desired dose to achieve steady state concentration Compute desired dose to achieve steady state concentration

12. Example time