02.04.2.2 Secretion and Reabsorption

In the adult there are about a million kidney tubules. In these tubules, movement out of the tubule into the interstitial fluid, and, hence, to the blood is known as reabsorption. Movement of substances into the tubules is known as secretion (Figure 2.8).

Figure 2.8 Reabsorption and secretion from kidney tubule (Copyright QUT, Sheila Doggrell)

Lipid soluble drugs are readily reabsorbed, so they will continue to be recycled back into circulation. It is only when drugs are water soluble that they remain in the kidney tubule to be excreted.

Endogenous compounds that are positively charged (choline, dopamine) are actively secreted into the proximal tubule using transporters. Many positively charged drugs can be secreted on these transporters (e.g. ranitidine), and are excreted following active transport into the urine. Similarly, endogenous compounds that are negatively charged are also secreted into the proximal tubule via transporters, and drugs can use this transporter. Drugs secreted using this transporter include the ACE inhibitor captopril.

The drug probenecid has two distinct actions on the kidney. The first action is related to uric acid. Uric acid (one of the body’s waste products) is actively reabsorbed from the kidney tubule, and an excessive accumulation of urate in the plasma leads to gout. The pain of gout is due to crystals of urate in the joints. Some drugs used to treat gout are known as uricosuric agents. The uricosuric agents (e.g. probenecid) inhibit the reabsorption to promote the excretion of urate, and prevent the accumulation of urate in joints. The second action of probenecid relates to penicillin levels. Penicillin is rapidly eliminated from the body, as 90% of penicillin is secreted into the proximal tubule, and excreted. Thus, after administration, the levels and effectiveness of penicillin declines rapidly. However, this can be inhibited by probenecid. Thus, probenecid can be used to increase and prolong the plasma levels of penicillin, to increase the effectiveness of penicillin.