The Absorption Concept

Under construction

The normal range for transit time includes the following:

• Gastric emptying (2–5 hours)
  • Generally assumed as 2 hours.
  • Highly diverse and primarily depend on whether the body is fed or fasted, and the size and density of the dosage form.
• Small intestine transit (2–6 hours)
  • Relatively constant, not affected much.
• Colonic transit (10–59 hours)
  • Influenced by a number of factors such as diet, stress, dietary fiber content and disease.
  • Diarrhea increases colonic transit, constipation decreases it.
  • Human activity can also affect dosage form motility in the colon, with the inactive state of sleep delaying the colonic transit.
• Whole gut transit (10–72 hours).

Drug absorption can be characterized by two pharmacokinetic parameters:

• Bioavailability ($\mathrm{F}$) quantifies the extent of absorption.
• ${\mathrm{k}}_{\mathrm{a}}$ quantifies the rate of absorption.

The oral bioavailability (F) of a drug is determined by three factors:

$$\begin{array}{}\text{(1)}& \mathrm{F}={\mathrm{f}}_{\mathrm{a}}\cdot {\mathrm{f}}_{\mathrm{g}}\cdot {\mathrm{f}}_{\mathrm{h}}={\mathrm{f}}_{\mathrm{a}}(1-{\mathrm{E}}_{\text{GI}})(1-{\mathrm{E}}_{\text{H}})\end{array}$$

where

• f_a is the fraction of drug absorbed,
  
• f_g is the fraction escaping gut-wall metabolism, and
  
• f_h is the fraction escaping hepatic extraction.

See Equation 1 and Figure 1 for an illustration of these processes.

$$\mathrm{F}=\left({\mathrm{AUC}}_{\text{po}}/{\mathrm{AUC}}_{\text{iv}}\right)\left({\mathrm{Dose}}_{\text{iv}}/{\mathrm{Dose}}_{\text{po}}\right)$$

Figure 1: Oral absorption.

Enterohepatic recirculation

Figure 2 depicts enterohepatic recirculation, which can also influence bioavailability. If a drug exhibits enterohepatic recirculation, it is common to see two or more absorption “peaks”.

Figure 2: Enterohepatic recirculation.

References