Valproic AcidValproic Acid

Software and Presentation by:Software and Presentation by:

Ted, Rob, Jeff, Cassie, Tristan, Korin, Ted, Rob, Jeff, Cassie, Tristan, Korin, Ron, Gabe, Matt, Judith, Lindsay Ron, Gabe, Matt, Judith, Lindsay

General InformationGeneral Information

Used in the management of multiple Used in the management of multiple seizure types.seizure types.

Oral and IV formsOral and IV formsAlso indicated for management of bipolar Also indicated for management of bipolar

affective disorder and possible migraine affective disorder and possible migraine prevention.prevention.

Increases body’s production and response Increases body’s production and response to GABA.to GABA.

Therapeutic / Toxic Conc’sTherapeutic / Toxic Conc’s

CpCpss ss range- 50 to 100 mcg/ml.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 At concentrations >75 mcg/ml some patients

may experience adverse effects.may experience adverse effects.

Basic Clinical PharmacokineticsBasic Clinical Pharmacokinetics

Exhibits concentration dependant protein bindingExhibits concentration dependant protein binding Follows Non-Linear KineticsFollows Non-Linear Kinetics

Highly protein bound to albuminHighly protein bound to albumin Follows a basic 1-Compartment Model.Follows a basic 1-Compartment Model.

Clinical ImplicationsClinical Implications

Clearance is now dose or concentration Clearance is now dose or concentration dependant. dependant.

Volume of Distribution is now affected by Volume of Distribution is now affected by concentration-dependant plasma protein concentration-dependant plasma protein binding and its value should be 0.15 to 2.0 binding and its value should be 0.15 to 2.0 L/kg.L/kg.

Half Life 12 to 18 hrs for adults and is Half Life 12 to 18 hrs for adults and is found by the eqn. tfound by the eqn. t1/21/2=0.693xVd/Cl =0.693xVd/Cl

Software StructureSoftware Structure Functional Functional

components of the components of the software were software were segmented into segmented into “tiers” to make the “tiers” to make the application to application to support ease of support ease of use and use and maintainabilitymaintainability CoreCore PeripheralPeripheral VariableVariable

Core

Core ComponentsCore Components Contains foundational Contains foundational

assumptions of the assumptions of the softwaresoftware User Input requirementsUser Input requirements Kinetic ModelsKinetic Models

Changing the Core will Changing the Core will cause global changes cause global changes to functionality and to functionality and require massive require massive reworking of the reworking of the systemsystem

Intolerant to changesIntolerant to changes

Core

Peripheral ComponentsPeripheral Components Contains slowly Contains slowly

changing parameterschanging parameters Changes cascade to Changes cascade to

most sections of the most sections of the softwaresoftware

Changes tolerated, but Changes tolerated, but should be rare and should be rare and hidden from most hidden from most usersusers

Provides extensibility Provides extensibility of the applicationof the application

Includes reports Includes reports charts, kinetic charts, kinetic parametersparameters

Core

Variable ComponentsVariable Components

Continuously Continuously changingchanging

High tolerance to High tolerance to changes, incorrect changes, incorrect / inappropriate / inappropriate inputinput

Patient CasesPatient Cases

Core

Bayesian PharmacokineticsBayesian Pharmacokinetics

Estimate drug dosage or steady state Estimate drug dosage or steady state plasma concentrationplasma concentration Patient’s parameters (age, weight, sex, serum Patient’s parameters (age, weight, sex, serum

creatine)creatine) Absence of or with measured drug levelsAbsence of or with measured drug levels

DrugCalc shareware softwareDrugCalc shareware softwareDr. Dennis MungallDr. Dennis MungallNonlinear regressionNonlinear regressionOne-compartment modelOne-compartment model

DrugCalc ExampleDrugCalc Example Enter patient’s demographic, Enter patient’s demographic,

drug dosing, and serum drug dosing, and serum concentrationconcentration

Compute the pharmacokinetic Compute the pharmacokinetic parametersparameters

Compute desired dose to Compute desired dose to achieve steady state achieve steady state concentrationconcentration

Example timeExample time