| Elimination of drugs from the body takes place in
much the opposite way as for drug absorption. Most drugs are eliminated by the kidneys, as a water soluble form of the
drug. Often the liver begins the process of preparing the drug molecule for
elimination and excretion by converting the molecule to a more water-soluble form of the
drug. Water soluble metabolites are formed. Ionized, water-soluble drug,
metabolites, and unionized drug courses through the body via the blood stream. At
the circulation to the kidneys, unionized drug may then pass from the blood through the
lipid membranes of the renal tubules to the urine. The kidney also has specialized
transport mechanisms for transporting ionized weak acids and bases from the blood to the
urine. If, on the other side of the membrane where urine is collected, the pH favors
the ionized, water-soluble form of the drug, the drug is excreted in the urine. If
conditions are favorable for the unionized form, the molecule may be reabsorbed back into
the circulation by passing back through the lipid membrane. The drug re-enters the
circulatory system, free to exert its therapeutic action once again.
So you can see how urine pH could have
an impact on the excretion of a drug. If the pH of the urine can be modified, it
would be possible then to prolong the effects of a drug by increasing the unionized form
in the urine (favoring reabsorption), or to expedite elimination by promoting the
excretion of the ionized form. Emergency room physicians often use this principle to
treat drug overdoses. |
