Azithromycin Aspartate

Aim In order to improve the solubility of azithromycin, the objectives of the present study were to screen an appropriate salt for azithromycin by comparing acute hepatic and renal toxicities in animals, and study the pharmacokinetics of final chosen azithromycin salt.Methods Various salts of azithromycin, such as glutamate, citrate, hydrochloride, sulfate, dihydrogen phosphate, lactobionate, tartrate, and aspartate were given i.v. to Sprague Dawley rats at a dose of 10 mg once daily for 14 consecutive days via tail vein.The acute hepatic and renal indicators were measured before and after administration.A pharmacokinetic study was performed on 12 healthy human volunteers.The subjects were equally divided into two groups by a randomized crossover design.Azithromycin glutamate injection was administered by i.v. infusion or i.m. injection at a single dose of 500 mg, resp.Azithromycin concentrations in plasma were determined by microbial inhibition zone assay, and the pharmacokinetic parameters were calculated using a practical pharmacokinetic software 3P87 program.Results Azithromycin glutamate was least toxic to the liver and kidney of the rats, thus being selected as a final salt for parenteral preparation of azithromycin.Pharmacokinetic results showed that the area under the plasma concentration-time curves (AUC_0-120 h) were 21.47±1.57 h·μg·mL^-1 for i.v. infusion, and 19.36±2.44 h·μg·mL^-1 for i.m. injection.The absolute bioavailability of i.m. injection was 92.59%.Conclusion Azithromycin glutamate is suitable for the future clin. application, and its pharmacokinetics is characterized in human volunteers in the present study.

The appropriate salt was used for azithromycin for injection.Eight different kinds of acid react to azithromycin to obtain corresponding azithromycin salt solutions and freeze-dried products for injection.The pH, initial stability and hepatic toxicity test in animals were performed.The solutions of glutamic acid, lactic acid, tartaric acid, and aspartic acid with azithromycin were stable and its pH was in proper range.The pathol. studies revealed that the favorable salts were glutamate, citrate, aspartate, sulfate and hydrochloride, followed by dihydrogen phosphate, lactobionate and tartrate.Glutamic acid and aspartic acid are the appropriate acid for the preparation for azithromycin for injection.