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Saturday, November 28, 2009

A Tale of Two Antibiotics, Part One

Ah, modern medicine...

Two antibiotics that I've had some recent experience with: the pharmacokinetically-curious macrolide, azithromycin, and the venerable (but still rather potent) tetracycline, doxycycline.


Azithromycin, commonly called 'Zithromax' or 'Z-Pak', is currently very popular as a broad-spectrum antibiotic that kills both Gram-positive (hard cell wall) and Gram-negative (outer membrane) bacteria. It does this by binding to the bacterial ribosome and interfering with the elongation step in protein synthesis, leading to cell degradation and death. Because bacterial and human ribosomes have slightly different structures, only bacterial cells are affected. Azithromycin is 'semisynthetic'; it is produced commercially by chemically-modifying erythromycin, another antibiotic that is produced by one species of actinomycete bacteria.

The odd thing about azithromycin: it is usually given as a single (rather gigantic) one-gram dose in powder form, but it remains effective for up to a week(!) afterwords. Like all macrolide antibiotics and many other drugs, azithromycin is involved in enterohepatic circulation: it is absorbed very readily in the small intestine and transported directly to the liver via the hepatic portal vein, where it is excreted in bile back into the duodenum (first section of the small intestine). For the chemical engineers out there, the hepatic portal-gall bladder-bile duct loop is just a recycle stream, and because it's running at a very high recycle ratio and the rate of azithromycin breakdown in the body is so low, it's easy to see how azithromycin can remain at therapeutic levels in the body for a long time on a single dose. Another form of recycle circulation further improves its half-life and effectiveness: azithromycin is preferentially taken up by white blood cells, which actively transport it to the site of infection and release it while consuming bacteria. Ion trapping and azithromycin's high lipid solubility keep its concentration at the infected site many times higher than in the blood plasma. Combined with its long half-life (68 hours) in the body and the fact that the patient doesn't have the option to discontinue the drug when they start feeling better, this helps to prevent the infecting bacteria from developing antibiotic resistance.

NEVERTHELESS, any given antibiotic will only kill certain bacteria. Azithromycin didn't work for me, so a week later I was back for a second round.

1 comment:

  1. Antibiotic recycle within the body would be a great example to write up for use in introductory Chemical Engineering material balances.

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