Module 1. Effect(s) of dose manipulation on plasma concentrations.

Objectives

Having completed this exercise and based on pharmacokinetic constants and data, students should be able to:

Significance

A veterinarian needs to appreciate the results of dose manipulation (in terms of plasma concentrations). Under normal circumstances doubling the dose doubles the plasma concentrations at all time points on the concentration versus time profile. This means that the pharmacokinetic constants do not change with a change in dose. This is what is meant by "dose independent pharmacokinetics". Certain misconceptions arise concerning the effect of increased dose on the duration of effect. It may seem logical to assume that doubling the dose of a drug will double its duration. In fact, doubling the dose of a drug usually extends its duration by one drug half-life.

Exercise

Download dose.xlsx, the worksheet for this module. Depending on your settings, you may have to "enable editing" in order to make the changes suggested by the exercise.

Pharmacokinetic variables on the worksheet are preset for a typical adult dog given an aspirin. Please note, the dose and interval were chosen for the purposes of this exercise and are not the only appropriate dose regimen for dogs.

Target concentrations

Manipulate the dosage

Inspect

Calculated values

Steady-State Concentrations (for repeated doses during therapy).

Graphs

Assess

Questions (Key)

  1. The model described in this exercise is dose independent. When dosage is changed in such a model, which of these does not change (list all that apply)? Cmax, Cave, Cmin, Clt, Vz, T1/2
  2. Assume that moderate analgesia requires a plasma concentration of 30 μg/ml. Based on the information in this module and for a dog, can an oral dose regimen for aspirin be designed to produce moderate analgesia without toxicity for an entire 12 hour dose interval?
  3. According to the plasma concentrations, how long was mild analgesia maintained after a 10 mg/kg oral dose? after a 20 mg/kg oral dose?
  4. Which calculated value conveniently approximates the increase in the length of time achieved (duration of a particular effect) when increasing the dose from 10 to 20 mg/kg?