A Textbook of Clinical Pharmacology and Therapeutics

ROUTES OF ADMINISTRATION

ORAL ROUTE

FOR LOCAL EFFECT

Oral drug administration may be used to produce local effects
within the gastro-intestinal tract. Examples include antacids,
and sulphasalazine, which delivers 5-amino salicylic acid
(5-ASA) to the colon, thereby prolonging remission in patients
with ulcerative colitis (Chapter 34). Mesalazine has a pH-
dependent acrylic coat that degrades at alkaline pH as in the

colon and distal part of the ileum. Olsalazine is a prodrug con-

sisting of a dimer of two 5-ASA moieties joined by a bond that is

cleaved by colonic bacteria.

FOR SYSTEMIC EFFECT

Oral administration of drugs is safer and more convenient for

the patient than injection. There are two main mechanisms of

drug absorption by the gut (Figure 4.4).

Passive diffusion

This is the most important mechanism. Non-polar lipid-soluble

agents are well absorbed from the gut, mainly from the small

intestine, because of the enormous absorptive surface area

provided by villi and microvilli.

Active transport

This requires a specific carrier. Naturally occurring polar

substances, including sugars, amino acids and vitamins, are

absorbed by active or facilitated transport mechanisms. Drugs

that are analogues of such molecules compete with them for

transport via the carrier. Examples include L-dopa, methotrex-

ate, 5-fluorouracil and lithium (which competes with sodium

ions for absorption).

Other factors that influence absorption include:

1. surgical interference with gastric function– gastrectomy
   reduces absorption of several drugs;
   2.disease of the gastro-intestinal tract(e.g. coeliac disease,
   cystic fibrosis) – the effects of such disease are
   unpredictable, but often surprisingly minor (see
   Chapter 7);
   3.the presence of food– the timing of drug administration in
   relation to meal times can be important. Food and drink
   dilute the drug and can bind it, alter gastric emptying and
   increase mesenteric and portal blood flow;

ROUTES OFADMINISTRATION 19

Passive diffusion of a

water-soluble drug

through an aquas

channel or pore

Passive diffusion

of a lipid-soluble

drug

Carrier-mediated

active transport

of drug

Lumen

Drug

Epithelial

cell

membrane

ATP

D

D

D

D D

D

D

D

D D

D

D

D

D

Figure 4.4:Modes of absorption of drugs

from the gut.

PRODRUG DRUG

Relatively well-

absorbed and/or

good tissue

penetration

INACTIVE

Various

enzymes

in body

Relatively poorly

absorbed and/or

poor tissue

penetration

ACTIVE
Figure 4.3:Clinical use of prodrugs.

Table 4.1:Prodrugs

Prodrug Product

Enalapril Enalaprilat

Benorylate Aspirin and paracetamol

Levodopa Dopamine

Minoxidil Minoxidil sulphate

Carbimazole Methimazole

Vanciclovir Aciclovir