AZITHROMYCIN- azithromycin monohydrate injection
To reduce the development of drug-resistant bacteria and maintain the effectiveness of azithromycin and other bacterial drugs, azithromycin for injection should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria.
Azithromycin for injection contains the active ingredient azithromycin, an azalide, a subclass of macrolide antibiotics, for intravenous injection. Azithromycin has the chemical name ( 2R,3S,4R,5R,8R,10R,11R,12S,13S,14R)-13-[(2,6-dideoxy-3- C -methyl-3- O -methyl-a-L- ribo -hexopyranosyl)oxy]-2-ethyl-3,4,10-trihydroxy-3,5,6,8,10,12,14-hepta-methyl-11-[[3,4,6-trideoxy-3-(dimethylamino)-ß- D -- xylo -hexopyranosyl]oxy]-1-oxa- 6-azacyclopentadecan-15-one. Azithromycin is derived from erythromycin; however, it differs chemically from erythromycin in that a methyl-substituted nitrogen atom is incorporated into the lactone ring. Its molecular formula is C38 H72 N2 O12 , and its molecular weight is 749. Azithromycin has the following structural formula:
Azithromycin, as the monohydrate, is a white crystalline powder with a molecular formula of C38 H72 N2 O12 .H2 O and a molecular weight of 767.
Azithromycin for injection consists of azithromycin monohydrate and the following inactive ingredients: citric acid and sodium hydroxide. Azithromycin for injection is supplied in lyophilized form in a 10 mL vial equivalent to 500 mg of azithromycin, 384.5 mg of citric acid, and sodium hydroxide for pH adjustment. Reconstitution, according to label directions, results in approximately 5 mL of azithromycin for intravenous injection with each mL containing 100 mg azithromycin (from azithromycin monohydrate).
In patients hospitalized with community-acquired pneumonia receiving single daily one-hour intravenous infusions for 2 to 5 days of 500 mg azithromycin at a concentration of 2 mg/mL, the mean Cmax ± S.D. achieved was 3.63 ± 1.60 mcg/mL, while the 24- hour trough level was 0.20 ± 0.15 mcg/mL, and the AUC24 was 9.60 ± 4.80 mcg•h/mL.
The mean C max , 24 hour trough and AUC24 values were 1.14 ± 0.14 mcg/mL, 0.18 ± 0.02 mcg/mL, and 8.03 ± 0.86 mcg•h/mL, respectively, in normal volunteers receiving a 3-hour intravenous infusion of 500 mg azithromycin at a concentration of 1 mg/mL. Similar pharmacokinetic values were obtained in patients hospitalized with community-acquired pneumonia that received the same 3-hour dosage regimen for 2 to 5 days.
|Plasma concentrations (mcg/mL ± S.D.) after the last daily intravenous infusion of 500 mg azithromycin|
|Infusion Concentration Duration||Time after starting the infusion (hr)|
|2 mg/mL, 1 hr *||2.98||3.63||0.60||0.40||0.33||0.26||0.27||0.20||0.20|
|1 mg/mL, 3 hr †||0.91||1.02||1.14||1.13||0.32||0.28||0.27||0.22||0.18|
|* = 500 mg (2 mg/mL) for 2-5 days in Community-acquired pneumonia patients. † = 500 mg (1 mg/mL) for 5 days in healthy subjects.|
The average CLt and Vd values were 10.18 mL/min/kg and 33.3 L/kg, respectively, in 18 normal volunteers receiving 1000 to 4000-mg doses given as 1 mg/mL over 2 hours.
Comparison of the plasma pharmacokinetic parameters following the 1st and 5th daily doses of 500 mg intravenous azithromycin showed only an 8% increase in Cmax but a 61% increase in AUC24 reflecting a threefold rise in C24 trough levels.
Following single oral doses of 500 mg azithromycin (two 250 mg capsules) to 12 healthy volunteers, Cmax , trough level, and AUC24 were reported to be 0.41 mcg/mL, 0.05 mcg/mL, and 2.6 mcg•h/mL, respectively. These oral values are approximately 38%, 83%, and 52% of the values observed following a single 500-mg I.V. 3-hour infusion (Cmax : 1.08 mcg/mL, trough: 0.06 mcg/mL, and AUC 24 : 5 mcg•h/mL). Thus, plasma concentrations are higher following the intravenous regimen throughout the 24 hour interval. The pharmacokinetic parameters on day 5 of azithromycin 250 mg capsules following a 500 mg oral loading dose to healthy young adults (age 18 to 40 years old) were as follows: Cmax : 0.24 mcg/mL, AUC24 : 2.1 mcg•h/mL. Azithromycin 250 mg capsules are no longer commercially available. Azithromycin 250 mg tablets are bioequivalent to 250 mg capsules in the fasting state.
Median azithromycin exposure (AUC 0-288 ) in mononuclear (MN) and polymorphonuclear (PMN) leukocytes following 1,500 mg of oral azithromycin, administered in single daily doses over either 5 days (two 250 mg tablets on day 1, followed by one 250 mg tablet on days 2 to 5) or 3 days (500 mg per day for days 1 to 3) to 12 healthy volunteers, was more than a 1000 fold and 800 fold greater than in serum, respectively.
All MedLibrary.org resources are included in as near-original form as possible, meaning that the information from the original provider has been rendered here with only typographical or stylistic modifications and not with any substantive alterations of content, meaning or intent.