Daily
use of calcium containing supplements (such as calcium carbonate) or
medications are fairly common and are known to be recommended by some medical
authorities.(1) Some patients may fail to disclose their use during a
review of medications at a clinic visit or upon admission to the hospital
because they may not consider the supplement to be a medication. Daily
administration of calcium carbonate is usually safe and appropriate, but
problems can arise when the patient develops an infection that requires the use
of the antibiotic, ciprofloxacin (Cipro). This is a very plausible
situation in both the outpatient setting and hospital setting. For
patients in the outpatient setting, it is common and maybe even desirable for
the patient to take all of their medications at one time. In the
hospital, administration of multiple medications simultaneously may also
desirable. Conversely, it may be that the scheduling of medication
administration is simply not given enough attention in regard to avoiding
combinations of drugs that should not be taken at the same time.
Regardless of the reason, the coadministration of calcium carbonate and
ciprofloxacin can result in a reduction in the absorption of ciprofloxacin by
an average of 40%.(2) Absorption can be further reduced if the gastric pH
is increased by other medications such as H2 receptor antagonists or proton
pump inhibitors.(3)
What
does calcium do to ciprofloxacin that results in this reduction in absorption
or bioavailability?
-
A basic evaluation of the chemical structure of ciprofloxacin reveals that each
ciprofloxacin molecule has one carboxyl group (R-COOH) as part of its structure.(4)
The important thing to note about this carboxyl group as it relates to an
interaction with calcium is its ionization state (i.e., whether it is chargedor uncharged). The carboxyl group becomes negatively charged when it
releases its hydrogen (H+) ion. This process is determined by its
pKa.
- The pKa for carboxyl groups is approximately 1.8 to 2.4.5
Therefore, a pH above this pKa would result in a greater percentage of the
carboxyl groups on ciprofloxacin being ionized (or in their negatively charged
state).
- Depending on other medications being taken by the patient (such
as antacids, H2 receptor antagonists or proton pump inhibitors) and the type of
food ingested, the pH of the stomach can easily range from 1 to 6; thus, it is
likely that the pKa of the carboxyl group will be exceeded.
- However, even
if the patient only takes the calcium carbonate along with the ciprofloxacin on
an empty stomach, the calcium carbonate itself can interact with hydrochloric
acid from the stomach to form calcium chloride, carbon dioxide and water and
cause an increase in the gastric pH. Therefore, the magnitude of change
in gastric pH (whether it is from calcium carbonate itself or from the
combination of calcium carbonate and other medications) will influence the amount
of ionized carboxyl groups found on ciprofloxacin.
- Once this ionization
has started to occur, the exposed and negatively charged group on ciprofloxacin
can then bind to the positively charged calcium (Ca++) ion that was present in
the medication or supplement administered.
- This final reaction is what
most clinicians refer to when they say that calcium or a cation (positively
charged molecule) can "chelate" ciprofloxacin. The degree or
significance of this interaction is, however, dependent on the time of their
exposure to one another and the pH of the environment at the time. A 2
hour separation of the calcium containing product and the ciprofloxacin can
avoid this interaction.6 Binding
or "chelation" of the ciprofloxacin with calcium will result in
decreased absorption or bioavailability of ciprofloxacin and potentially
increase the risk for treatment failure of the infection.
- The risk of
failure to treat the infection will obviously also be influenced by the minimum
inhibitory concentration (MIC) of the bacteria and the tissue being targeted.
