Azithromycin
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Azithromycin is an azalide, a subclass of macrolide antibiotics. Azithromycin is derived from erythromycin; however, it differs chemically from erthyromycin in that a methyl-substituted nitrogen atom is incorporated into the lactone ring, thus making the lactone ring 15-membered. Azithromycin is sold under the brand names Zithromax ("Zmax") and Sumamed, and is one of the world's best-selling antibiotics. Azithromycin is used to treat certain bacterial infections, most often bacteria causing middle ear infections, tonsillitis, throat infections, laryngitis, bronchitis, pneumonia and sinusitis. It is also effective against certain sexually transmitted infectious diseases, such as nongonococcal urethritis and cervicitis.
| Image:Azithromycin.png Azithromycin | |
| 9-deoxy-9a-aza-9a-methyl-9a- homoerythromycin A | |
| Molecular Weight | 748.88 |
| Empiric Formula | C38H72N2 O12 |
| ATC code | J01FA10 |
| Bioavailability | 38% for 250mg capsules |
| Metabolism | hepatic |
| Excretion | biliary, renal |
| Half-life | 68 hours |
| Pregnancy category | B (USA) B1 (Aus) |
Contents |
Etymology
Azithromycin's name is derived from the azane-substituent and erythromycin. Its accurate chemical name is
(2R,3S,4R,5R,8R,10R,11R,12S,13S,14R)-13- [(2,6-dideoxy-3-C-methyl-3-O-methyl -α-L-ribo-hexopyranosyl)oxy]-2-ethyl- 3,4,10-trihydroxy-3,5,6,8,10,12,14-heptamethyl -11-[[3,4,6-trideoxy-3-(dimethylamino) -β-D-xylo-hexopyranosyl]oxy]-1-oxa- 6-azacyclopentadecan-15-one.
History
A team of Pliva's researchers, Gabrijela Kobrehel, Gorjana Radobolja-Lazarevski and Zrinka Tamburasev led by Dr Slobodan Dokic, discovered azithromycin in 1980. It was patented in 1981, and was later found by Pfizer's scientists while going through patent documents. In 1986 Pliva and Pfizer signed a licensing agreement which gave Pfizer exclusive rights for the sale of azithromycin in Western Europe and the United States. Pliva brought their azithromycin on the market in Central and Eastern Europe under the brand name of Sumamed in 1988, and Pfizer Zithromax in 1991.
Available forms
Azithromycin is commonly administered in tablet or oral suspension (a one-dose version was made available in 2005). It is also available for intravenous injection. Tablets come in 250mg and 500mg doses. Oral suspension comes in 100mg/teaspoon and 200mg/teaspoon stengths. When administered as a single dose, 2 grams is usually taken.
Azithromycin tablets are mottled pink, unscored, film-coated, modified-oval-shaped tablets containing azithromycin monohydrate equivalent to 250mg or 500mg azithromycin and the following inactive ingredients: butylated hydroxytoluene, calcium phosphate dibasic anhydrous, carmine, colloidal silicone dioxide, FD&C red # 40 lake, FD&C yellow # 6 lake, hypromellose (2910, 15cP), lactose monohydrate, magnesium strearate, pregelatinized starch, sodium lauryl sulfate, talc, titanium dioxide and triacetin.
Microbiology
Azithromycin prevents bacteria from growing by interfering with their protein synthesis. Azithromycin binds to the 50S subunit of the bacterial ribosome, and thus inhibits translation of mRNA. Nucleic acid synthesis is not affected. Azithromycin has similar antimicrobial spectrum as erythromycin, but is more effective against certain gram-negative bacteria, particularly Haemophilus influenzae.
Azithromycin has been proven to be most effective against the most isolates of the following microorganisms:
- Staphylococcus aureus
- Streptococcus agalactiae
- Streptococcus pneumoniae
- Streptococcus pyogenes
- Haemophilus ducreyi
- Haemophilus influenzae
- Moraxella catarrhalis
- Neisseria gonorrhoeae
- Chlamydia pneumoniae
- Chlamydia trachomatis
- Mycoplasma pneumoniae
Pharmacokinetics
Unlike erythromycin, azithromycin is acid-stable and can therefore be taken orally with no need of protection from gastric acids. It is readily absorbed, and diffused into most tissues and phagocytes. Due to the high concentration in phagocytes, azithromycin is actively transported to the site of infection. During active phagocytosis, large concentrations of azithromycin are released. The concentration of azithromycin in the tissues can be over 50 times higher than in plasma. This is due to ion trapping and the high lipid solubility.
Metabolism
Following a single 500mg dose, plasma concentrations of azithromycin declined in a polyphrasic pattern with a mean apparent plasma clearance of 630mL/min and a terminal elimination half-life of 68 hours. The prolonged terminal half-life is thought to be due to extensive uptake and subsequent release of drug from tissues.
Biliary excretion of azithromycin, predominately unchanged, is a major route of elimination. Over the course of a week, approximately 6% of the administered dose appears as unchanged drug in urine.
Side effects
Most common side effects are gastrointestinal; diarrhea, nausea, abdominal pain and vomiting. Serious allergic reactions, dermatologic reactions, and fatalities have been reported but are extremely rare.