Chapter 8

Pharmacokinetics of Oral Administration

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Pharmacokinetics of Oral Administration

Student Objectives for this Chapter

• be able to draw the scheme and write the differential equations for a one compartment pharmacokinetic model with first order absorption
• be able to use the integrated equations for this pharmacokinetic model to calculate parameter values and dosing regminens
• be able to define, use, and calculate the parameters:
  • absorption rate constant, ka
  • fraction absorbed, bioavailability, F
  • time of peak concentration, t_peak
  • maximum plasma concentration, Cp_max
• be able to describe the effect of changing ka and/or F values on plasma concentration versus time curves including
  • with altered liver function on first-pass metabolism
  • with improved drug absorption through reformulation
  • with different dosage forms such solution, tablets and controlled release tablets

So far we have considered the pharmacokinetics of intravenously administered drugs, either as a bolus or by infusion. If we know kel and V for a particular patient we can calculate appropriate doses or dosing rates (infusion rates) to produce the necessary therapeutic concentrations.

In the previous Chapter we considered a number of routes of drug administration. Most of the routes of administration were extravascular; for example IM, SC, and most importantly oral. With these types of drug administration the drug isn't placed in the central compartment but must be absorbed through at least one membrane. This has a considerable effect on drug pharmacokinetics and may cause a reduction in the actual amount of drug which is absorbed.

Most commonly the absorption process follows first order kinetics. Even though many oral dosage forms are solids, which must dissolve before being absorbed and absorption may occur at various parts of the GI tract, the overall absorption process can often be considered to be a single first order process. At least that's the assumption we will use for now.

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