Azithromycin

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Azithromycin
Systematic (IUPAC) name
9-deoxy-9a-aza-9a-methyl-9a- homoerythromycin A
Identifiers
CAS number	83905-01-5
ATC code	J01 FA10
PubChem	55185
Chemical data
Formula	C₃₈H₇₂N₂O₁₂
Mol. weight	748.88
Pharmacokinetic data
Bioavailability	38% for 250mg capsules
Metabolism	hepatic
Half life	68 hours
Excretion	biliary, renal
Therapeutic considerations
Pregnancy cat.	B (USA) B1 (Aus)
Legal status
Routes	oral (capsule)

Azithromycin is an azalide, a subclass of macrolide antibiotics. Azithromycin (brand names Zithromax® in Italy; Vinzam® / Zitromax® in Spain; Zmax®; Sumamed®; Aztrin®) is one of the world's best-selling antibiotics, and is derived from erythromycin; however, it differs chemically from erythromycin in that a methyl-substituted nitrogen atom is incorporated into the lactone ring, thus making the lactone ring 15-membered. 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 non-gonococcal urethritis and cervicitis. Recent studies have also shown it to be effective against late-onset asthma, but these findings are controversial and not widely accepted as of yet.

1 Etymology
2 History
3 Available forms
4 Microbiology
5 Pharmacokinetics
6 Metabolism
7 Side effects
8 Reference links
9 External links

[edit] 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.

[edit] 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.

[edit] 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. The 250mg tablets are often dispensed in packages of six and commonly referred to as a "Z-Pak," whereas the 500mg tablets are commonly available commercially in a pack of three tablets, or "Tri-Pak," intended as a three-day treatment. A common dose of oral azithromycin therapy consists of a "double dose" of medication on the first day of treatment and subsequent treatment for four or five additional days. With the "Z-Pak," this means two 250mg tablets (a total of 500mg) on the first day and one 250mg tablet once daily for the next four days.

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, carmine, colloidal silicon dioxide, FD&C red # 40 lake, FD&C yellow # 6 lake, hypromellose (2910, 15cP), lactose monohydrate, magnesium stearate, pregelatinized starch, sodium lauryl sulfate, talc, titanium dioxide and triacetin. The 250mg tablets have the following appearance: they are mottled pink, of a modified-oval-shape, and have "Pfizer" engraved into one side with "306" engraved into the other. The 500mg tablet is similar in appearance with the exception of its relative size and "ZTM500" engraved onto one side with "Pfizer" on the reverse. As with all medications, generic azithromycin tablets produced by companies other than Pfizer without the Zithromax brand name may have different appearances, but they tend to share the same general shape and coloration.

[edit] 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:

[edit] 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.

[edit] 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.

[edit] 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. As with all antimicrobial agents, pseudomembranous colitis can occur during and up to several weeks after azithromycin therapy.