antibioticsbooks

chapter 3 Pharmacokinetics 27
can be similar to, lower than, or greater than the
concentration of the antibiotic in the blood. A consequence
is that a drug may be more or less effective
in a particular tissue than would be expected
based on its concentrations in the blood. For example,
the concentrations of antibiotics in the cerebrospinal
fluid are typically much lower than their
bloodstream concentrations, limiting the effectiveness
of many antibiotics in the treatment of meningitis.
On the other hand, the macrolide antibiotics
are more effective in lung infections than may be
anticipated based on their blood levels, because
they concentrate in pulmonary macrophages. With
a few exceptions such as cerebrospinal fluid, it
is difficult to obtain samples of human tissues to
determine antibiotic concentrations, and it is technically
difficult to measure the concentrations in
tissues like bone. Thus, data on drug distribution
are often extrapolated from animal models, which
may or may not be good surrogates for humans.
The extent to which antibiotics distribute into
different tissues is largely determined by the physicochemical
properties of the drug (lipophilicity,
charge, molecular size, etc.). A key determinant
of distribution is the degree to which an antibiotic
binds to proteins in the bloodstream, most
importantly albumin (you may hear this expressed
as “fraction bound” or “fraction unbound”). Drug
bound to proteins is not able to diffuse across membranes
into different tissues; thus, antibiotics that
are highly protein bound may be less likely to reach
effective concentrations in certain tissues (such as
the central nervous system). It is important to realize
that the percentage degree of penetration of an
antibiotic into a tissue is not the only determinant