Module 7. Effect of route of administration and dose form on the performance (clinical effect) of drug products.

Objectives

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

Significance

J.F.M. Nouws et al: Comparative plasma ampicillin levels and bioavailability of five parenteral ampicillin formulations in ruminant calves.

Route of administration and dose form affect the performance (clinical effect) of drug products. Ampicillin sodium is labeled for intravenous and intramuscular use. Ampicillin trihydrate is labeled for intramuscular use only. Your choice of drugs should be based on the performance characteristics you desire in addition to the labeled route and the price of the penicillin product. This exercise demonstrates that, for Ampicillin at least, drug concentrations may be affected more by dose form than by route of administration.

When ampicillin was originally approved (and the label dose was created) it is likely that gram (-) organisms were in fact, more susceptible to ampicillin. Target concentrations represent information not widely discussed when ampicillin was approved, but it is likely that gram negative organisms have become more resistant.

It would appear that ampicillin remains a viable drug for gram (+) infections. This does not say that resistance to ampicillin in certain gram positive populations is not a problem.

Exercise

Download ampicillin.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 ruminant calves and specific dose forms and routes.

You need not change the pharmacokinetic settings for this exercise.

Target concentrations

Manipulate the dosage

Inspect

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

Graphs

Assess

Questions (Key)

  1. What two pharmacokinetic constants account for the differences between Na ampicillin and ampicillin trihydrate given intramuscularly?
  2. If the pharmacokinetic model is dose independent (as implied in this module and the associated worksheet), doubling the dose (same interval) should double the steady state concentrations. It is actually quite likely that the absorption kinetics of ampicillin trihydrate are dose dependent. If this is so, doubling the dose should produce
    1. more than a doubling of the steady state concentrations.
    2. less than a doubling of steady state concentrations.
  3. A clinical patient of yours has received several doses of IV Ampicillin sodium (for a suspected gram negative infection) and appears to be responding. Your technician informs you that "no more veins are available". Do you choose IM Ampicillin sodium (#2) or IM Ampicillin trihydrate (#3) to acheive the SAME clinical effect?
  4. Based on your answer for question 3, do you need to give a larger total dose or can it remain approximately the same?