Drug Absorption
Lester Sultatos New Jersey Medical School, Newark, USA
ã 2007 Elsevier Inc. All rights reserved.
Drug absorption is the movement of a drug from its site of application into the blood-
stream. Unless a drug is directly applied to, or in the vicinity of, the target site, absorption
must occur for a drug to exert its therapeutic effect. For drugs applied at their target, such
as local anesthetics, absorption often terminates the therapeutic effect. As drug absorp-
tion usually occurs by passive diffusion across membranes, the basic principles govern-
ing absorption are similar to those governing distribution. Because biological membranes
contain a lipid core, they represesnt a lipophilic environment. Consequently, the rate at
which drugs diffuse through membranes is directly related to their relative degree of lipid
solubility. Thus, lipid soluble agents usually pass readily through membranes, and more
water-soluble drugs do so more slowly, if at all. As a result, lipid soluble drugs tend to be
absorbed more quickly than water-soluble agents.
For a drug to be absorbed, it must either be a liquid or dissolved in solution. When
considering the dissolution of drugs in water, there are two general categories of drugs:
those that are neutral in solution and those that ionize in solution (weak acids and weak
bases). The ability of neutral drugs to cross membranes by passive diffusion is strictly a
function of their relative lipid solubility. However, for weak acids or weak bases, the
degree of ionization contributes significantly to their ability to cross membranes by
passive diffusion. A weak acid is defined as a compound that releases hydrogen ions
(protons) in solution, whereas a weak base is one that accepts hydrogen ions. Functional
groups for drugs that often ionize are:
The degree of ionization of a drug in solution is a function of (1) whether it is a weak
acid or weak base, (2) the pH of the aqueous phase, and (3) the pKa of the compound. The
pKa is defined as the pH at which half of the molecules in solution are ionized and half are
unionized. The degree of ionisation is calculated from the Henderson Hasselbalch
equation:
pH-pKa = Log(Base(A-)/Acid(HA)
The application of this equation is shown below for aspirin, a weak acid with a pKa of
3.49.
1
2 Drug Absorption
Thus, at a pH of 3.49, the pKa of aspirin, 50% of the compound in solution is in the
unionized form and 50% is in the ionized form. Accordingly, in an acidic environment,
such as in the stomach, aspirin is mostly unionised, and therefore, some absorption could
occur in this tissue as a result of passive diffusion. Conversely, at a pH of 7.4, most aspirin
molecules are ionized and, therefore, diffuse less readily across membranes.
As illustrated above, when weak acids are at a pH below their pKa, most of the molecules
are in the unionized form, whereas at a pH above their pKa, most of the molecules are
in the ionized form. The opposite holds for weak bases. In this case, at a pH above their
pKa (also sometimes referred to as the pKb for bases), most of the molecules are in the
unionized form, whereas at a pH below their pKa, most of the molecules are in the ionized
form.
Absorption of drugs occurs from many sites. Administration through the alimentary
canal is referred to as enteral, and all other routes are parenteral (see the record on Drug
Absorption from the Gastrointestinal Tract).
Other Information – Web Sites
http://www.merck.com/pubs/mmanual/section22/chapter298/298a.htm This is an open
access website that discusses absorption, distribution, biotransformation, and excretion of
drugs.
http://cellbio.utmb.edu/cellbio/membrane.html This is an open access website that
describes the structure and function of membranes.
Further Reading
Introduction, In: B. G. Katzung (Ed.), Basic and Clinical Pharmacology, Edition 8, McGraw-Hill, New York,
2001, pp. 1–8
Holford, N.H.G, Pharmacokinetics and Pharmacodynamics: Rationale Dosing and the Time Course of Drug
Action, In: B. G. Katzung (Ed.), Basic and Clinical Pharmacology, Edition 8, McGraw-Hill, New York, 2001,
pp. 35–50
Yagiela, J.A., Pharmacokinetics: the Absoprtion, Distribution, and Fate of Drugs, In: J. A. Yagiela,
F. A. Neidle and F. J. Dowd (Eds.), Pharmacology and Therapeutics for Dentistry, Edition 4, Mosby, St.
Louis, MO, 1998, pp. 15–41
Wilkinson, G.R., Pharmacokinetics: The Dynamics of Drug Absorption, Distribution, and Elimination, In:
J. G. Hardman and L. E. Limbird (Eds.), Goodman and Gilman’s The Pharmacological Basis of
Therapeutics, Edittion 10, McGraw-Hill, New York, 2001, pp. 3–29
