Valproic Acid

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Valproic Acid

• Software and Presentation by
• Ted, Rob, Jeff, Cassie, Tristan, Korin, Ron,
  Gabe, Matt, Judith, Lindsay

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General Information

• Used in the management of multiple seizure types.
• Oral and IV forms
• Also indicated for management of bipolar
  affective disorder and possible migraine
  prevention.
• Increases bodys production and response to GABA.

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Therapeutic / Toxic Concs

• Cpss range- 50 to 100 mcg/ml.
• Upper limit of 175mcg/ml with proper monitoring.
• At concentrations gt75 mcg/ml some patients may
  experience adverse effects.

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Basic Clinical Pharmacokinetics

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

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Clinical Implications

• 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.
• Half Life 12 to 18 hrs for adults and is found by
  the eqn. t1/20.693xVd/Cl

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Software Structure

• Functional components of the software were
  segmented into tiers to make the application to
  support ease of use and maintainability
• Core
• Peripheral
• Variable

Core
Peripheral
Variable
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Core Components

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

Core
Peripheral
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Peripheral Components

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

Peripheral
Core
Peripheral
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Variable Components

• Continuously changing
• High tolerance to changes, incorrect /
  inappropriate input
• Patient Cases

Core
Peripheral
Variable
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Bayesian Pharmacokinetics

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

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DrugCalc Example

• Enter patients demographic, drug dosing, and
  serum concentration
• Compute the pharmacokinetic parameters
• Compute desired dose to achieve steady state
  concentration

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Example time