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Azithromycin dosage forms with reduced side effectsRelated Patent Categories: Organic Compounds -- Part Of The Class 532-570 Series, Azo Compounds Containing Formaldehyde Reaction Product As The Coupling Component, Carbohydrates Or Derivatives, O- Or S- Glycosides, Oxygen Containing Hetero Ring Having 12-19 Members (e.g., Methymycin, Carbomycin, Spiramycin, Etc.)Azithromycin dosage forms with reduced side effects description/claimsThe Patent Description & Claims data below is from USPTO Patent Application 20080015343, Azithromycin dosage forms with reduced side effects. Brief Patent Description - Full Patent Description - Patent Application Claims
[0001] This application is a divisional application of U.S. Ser. No. 10/763,340, filed on Jan. 23, 2004 which is a nonprovisional application of provisional application Ser. No. 60/527,084, filed Dec. 4, 2003. BACKGROUND OF THE INVENTION [0002] Azithromycin is an antibiotic which is administered orally or intravenously, to treat various infections, particularly infections of the urinary tract, bronchial tract, lungs, sinuses and the middle ear. [0003] Oral dosing of azithromycin can result in adverse gastrointestinal (GI) side effects such as nausea, cramping, diarrhea and vomiting in a significant number of patients. Such GI side effects can also occur in non-human mammals, e.g., dogs. In combined clinical studies of azithromycin involving 3,995 human patients (all dose levels combined), 9.6% of patients reported GI side effects; the most frequent of these side effects were diarrhea (3.6%), nausea (2.6%), and abdominal pain (2.5%) Hopkins, 91 Am. J. Med. 40S (suppl 3A 1991). [0004] The frequency of these adverse effects increase with higher dose levels of azithromycin. In treating adult humans, for a single 1 gram dose, administered in an oral suspension, the reported incidence of various GI side effects was 7% diarrhea/loose stools, 5% nausea, 5% abdominal pain, and 2% vomiting (U.S. Package Insert for Zithromax.RTM. azithromycin for oral suspension). However, for a single 2 gram, administered in an oral suspension, the reported incidence of various GI side effects was 14% diarrhea/loose stools, 7% abdominal pain, and 7% vomiting (Ibid.). [0005] Similarly, in treating pediatric humans, by administering an oral suspension containing 10 mg/kg on Day 1 and 5 mg/kg on days 2-5, the reported incidence of various GI side effects was 4% diarrhea/loose stools, 2% abdominal pain, and 2% vomiting (Ibid.), while, for a single 30 mg/kg dose, administered in an oral suspension, the reported incidence of various GI side effects was 6.4% diarrhea/loose stools, 1.7% nausea, and 4% vomiting (Ibid.). [0006] Antacids, which are alkalizing agents that are provided in large doses to raise stomach pH from about 1-3 to about 4-7, may provide a patient with relief from diarrhea, cramping, and gastric upset. However, patients have been cautioned against simultaneously taking an antacid, particularly those containing aluminum or magnesium, with azithromycin, as antacids have been shown to reduce azithromycin maximum serum concentration C.sub.max by 24% (Ibid.). Further, to avoid antacid caused interference with azithromycin absorption, patients have also been advised to separate the administration of azithromycin and antacid doses by at least two hours. [0007] Presently, small amounts, about 132 mg or less, of the alkalizing agent anhydrous tribasic sodium phosphate are used in commercial dosage forms of azithromycin to mask the bitter taste of azithromycin by reducing the solubility of azithromycin before swallowing. Further, in treating uncomplicated gonococcal infections, two single dose packets of azithromycin, which each contain 88 mg of anhydrous tribasic sodium phosphate, are concurrently administered in a single dose to a patient in need thereof. [0008] More recently, azithromycin controlled release dosage forms have been prepared, as described in U.S. Pat. No. 6,068,859, that reduce the gastrointestinal side effects, resulting from an administered dose of azithromycin, as compared to an equivalent dose of commercial immediate release azithromycin capsules. However, the bioavailability of many of the controlled release dosage forms, specifically exemplified therein, were subsequently found to be less than their immediate release equivalents. [0009] Therefore, what is needed is an azithromycin dosage form that has a bioavailability similar to, and gastrointestinal side effects less than, an equivalent dose of immediate release azithromycin. SUMMARY OF THE INVENTION [0010] The present invention relates to an oral dosage form of azithromycin comprising azithromycin and an effective amount of an alkalizing agent. Preferably, said oral dosage form comprises an effective amount of an alkalizing agent and an azithromycin multiparticulate wherein said multiparticulate comprises azithromycin, a mixture of glyceryl mono-, di- and tribehenates, and a poloxamer. [0011] The present invention further relates to an oral suspension comprising azithromycin, an effective amount of an alkalizing agent and a vehicle. Preferably, the azithromycin is in multiparticulate form. More preferably, the multiparticulates comprise azithromycin, a mixture of glyceryl mono-, di- and tribehenates, and a poloxamer. [0012] Even more preferably, the azithromycin oral dosage form and oral suspension further comprise 300 mg to 400 mg of tribasic sodium phosphate, 200 mg to 300 mg of magnesium hydroxide, and multiparticulates, wherein said multiparticulates comprise (i) azithromycin, (ii) a mixture of glyceryl monobehenate, glyceryl dibehenate and glyceryl tribehenate, and (iii) poloxamer 407, and wherein said dosage form contains about 1.5 gA to about 4 gA of azithromycin. [0013] In addition, the present invention also relates to a method for reducing gastrointestinal side effects, associated with administering azithromycin to a mammal, comprising contiguously administering azithromycin and an effective amount of alkalizing agent to said mammal wherein the frequency of gastrointestinal side effects is lower than that experienced by administering an equal dose of azithromycin without said alkalizing agent. In this method, it is preferable that the multiparticulates comprise (i) azithromycin, (ii) a mixture of glyceryl monobehenate, glyceryl dibehenate and glyceryl tribehenate, and (iii) a poloxamer. [0014] The present invention further relates to a method of treating a bacterial or protozoal infection in a mammal in need thereof comprising contiguously administering to said mammal an oral dosage form wherein said oral dosage form comprises azithromycin and an effective amount of an alkalizing agent. Preferably, in this method, between 250 mgA and 7 gA of azithromycin are administered to a human. More preferably, 1.5 gA to 3 gA of azithromycin are administered to a human, even more preferably in a single dose. Also more preferably, for a pediatric human weighing 30 kg or less, between 45 mgA/kg and 75 mgA/kg of azithromycin are administered to said child, even more preferably in a single dose. [0015] The present invention additionally relates to azithromycin multiparticulates comprising azithromycin, a surfactant; and a pharmaceutically acceptable carrier. BRIEF DESCRIPTION OF THE DRAWINGS [0016] FIG. 1, which is further discussed in Example 1, shows the effects on pH of titrating different alkalizing agents with increasing volumes of 0.1N HCl. [0017] FIG. 2, which is further discussed in Examples 1 and 8, shows the calculated pH of different alkalizing agents when titrated with 0.1N HCl over time. [0018] FIG. 3, which is further discussed in Example 8, shows the calculated pH of different alkalizing agents when titrated with 0.1N HCl over time. DETAILED DESCRIPTION OF THE INVENTION [0019] As used in the present invention, the term "about" means the specified value .+-.10% of the specified value. [0020] As used in the present invention, the terms "a" or "an" mean one or more. For example, the term "an alkalizing agent" means one or more alkalizing agents, the term "a carrier" means one or more carriers, and the term "a dissolution enhancer" means one or more dissolution enhancers. Continue reading about Azithromycin dosage forms with reduced side effects... Full patent description for Azithromycin dosage forms with reduced side effects Brief Patent Description - Full Patent Description - Patent Application Claims Click on the above for other options relating to this Azithromycin dosage forms with reduced side effects patent application. ###  How KEYWORD MONITOR works... a FREE service from FreshPatents1. Sign up (takes 30 seconds). 2. Fill in the keywords to be monitored. 3. Each week you receive an email with patent applications related to your keywords. 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