College of Pharmacy

7 Greenhouse Road Kingston, RI 02881

pharmcol@etal.uri.edu – Office: 401.874.2761 Fax: 401.874.2181

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Clinical Pharmacokinetics and Pharmacodynamics

Sara Rosenbaum, Ph.D.

Located in Lab Module 495 on Level 4 of the Pharmacy building

IMODR: Basic Pharmacokinetic and Pharmacodynamic Models

The models presented here are incorporated into the textbook, Basic Pharmacokinetics and Pharmacodynamics: An Integrated Textbook with Computer Simulations, S.E. Rosenbaum, John Wiley, Inc Hoboken, NJ,  (2011). The chapter in the textbook corresponding to each model is shown in  parenthesis.

iMODR: Flash-Based Models and Videos

iMODR: Custom Models

 


chapter2

Transporter Model (Chapter 2)

The direction of the change in Cp is in keeping with the transporter’s function at each site. The magnitude of the change in Cp has been  arbitarily selected for clarity: absorption and excretion transporters were programed to produce about  a 2 fold change in F and renal clearance respectively

chapter7

IV Bolus Injection in a One Compartment Model (Chapter 7)

1. Observe the structure of the one compartment model with single IV bolus input   2. Observe how Cp changes over Time 3. Observe how the primary pharmacokinetic parameters, CL and Vd, influence the Cp-Time profile

chapter8

IV Bolus Injection in a Two Compartment Model (Chapter 8)

1. Understand the physiological basis for the 2-compartment model 2.Observe the characteristics of the Cp-Time profile 3.Understand how the primary PK parameters influence the Cp-Time profile

chapter9

Characteristics of First Order Absorption in a One Compartment Model (Chapter 9)

1. Understand the Cp-Time profile observed from extravascular drug administration 2. Understand how the absorption rate constant (ka) and the fraction of the dose  absorbed (F) influence the Cp-time profile . Understand the Flip-Flop model . Appreciate the significance of the bioavailability parameters

chapter11a

Intravenous Infusion: Constant Continuous Administration (Chapter 11)

1. Understand the pharmacokinetic characteristics of extended drug administration 2. Appreciate how clearance and volume of distribution impact the Cp-time profile 3. Determine administration rates to achieve desired steady state concentrations 4. Gain experience determining a loading dose 5. Observe the Cp-time profile after termination of the infusion

chapter11b

The Infusion Challenge (Chapter 11)

CHARGE: Use population average PK and PD parameters to determine the initial rate of drug administration for a patient. Evaluate the potential need to modify the rate of administration when you are informed through phone calls, Emails and text messages of changes in the patient’s status.

chapter13

Multiple IV Bolus Injections (Chapter 12)

1. Understand the Cp-Time profile observed from multiple IV doses 2. Understand the determinants of fluctuation and accumulation 3. Appreciate how Cl and Vd effect the Cp-Time profile

basicmodels_clip_image001

Multiple Intermittent Short Infusions (Chapter 13)

1. Observe Cp-Time profile associated with multiple short  intermittent infusions 2. Observe how the duration of the infusion influences the Cp-Time profile 3. Practice designing dosing regimens to achieve desired peaks and troughs

chapter14

Multiple Oral Doses (Chapter 14)

1. Understand the Cp-Time profile observed from multiple oral doses, with special emphasis on steady state 2. Appreciate the impact of the rate and extent of absorption on the Cp-time profile  3. Appreciate how the relationship between tau and t1/2 influences  fluctuation

chapter15

Nonlinear Pharmacokinetics (Chapter 15)

1. Using phenytoin as an example, understand a model for capacity limited elimination 2. Observe how increases in the rate of administration affect Cp 3. Understand how Vmax and Km influence the Cp-Time profile

chapter16

Sigmoidal Emax Model (Chapter 16)

1. Introduce the characteristics of the Sigmoidal Emax and Emax models 2. Compare the time course of Cp and Response after a dose 3. Illustrate how pharmacodynamics can influence a drug’s duration of action 4. Illustrate the impact of the slope or sigmoidicty factor ‘n’

chapter16b

Sigmoidal Emax Model With an Effect Compartment (Chapter 16)

1. Demonstrate how an effect compartment can be linked to a PK and PD model 2. Illustrate hysteresis 3. Illustrate the importance of keo

chapter17a

Operational Model of Agonism (Chapter 17)

1. Observe how the OMA can be used to assess drug efficacy in-vivo. 2. Observe how a drug’s efficacy in a system depends on the concentration of working receptors in the system. 3. Observe how the transduction ratio can be used to assess efficacy.

chapter17b

Indirect Effect Model I: Inhibition in kin (Chapter 17)

1. Understand the structure of the indirect model 2. Understand the influence of model parameters on response 3. Appreciate the factors that control the onset magnitude and duration of response

chapter17c

Indirect Effect Model II: Inhibition of kout (Chapter 17)

1. Understand the structure of the indirect model 2. Understand the influence of model parameters on response 3. Appreciate the factors that control the onset magnitude and duration of response

chapter17d

Indirect Effect Model III: Stimulation of kin (Chapter 17)

1. Understand the structure of the indirect model 2. Understand the influence of model parameters on response 3. Appreciate the factors that control the onset magnitude and duration of response

chapter17e

Indirect Effect Model IV: Stimulation of kout (Cchapter 17)

1. Understand the structure of the indirect model 2. Understand the influence of model parameters on response 3. Appreciate the factors that control the onset magnitude and duration of response

chapter17f

Transit Compartment (Chapter 17)

1. Understand the characteristics of the transit compartment model 2. Observe how the response profile changes between compartments 3. Observe how the response is influenced by the dose 4. Observe how the response is influenced by the number of compartments and by the total mean transit time

chapter17g

Hypothetical Antagonist Model For Tolerance (Chapter 17)

1. Use the model for nicotine’s effect on heart rate to demonstrate how tolerance    can be modeled using a hypothetical metabolite that acts as a drug antagonist 2. Observe how the model can be used to understand the time course of     tolerance and to plan compensatory strategies to minimize drug tolerance

chapter17j

Hematological Toxicity of Anticancer Drugs (Chapter 17)

1. Present the structure of a PD model for the hematological toxicty 2. Observe the onset, duration of, and recovery from, drug-induced neutropenia 3. Observe how a drug’s PK and PD effects the duration and intensity of neutropenia

chapter17i

Irreversible Effects (Chapter 17)

1. Understand how irreversible drug effects can be modeled 2. Observe the time course of plasma concentrations and response 3. Using a simulation model based on disolvprazole (see text), observe how     irreversible drug effects impact the design of dosing regimens

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