title: Prediction of the stability of imipenem in intravenous mixtures.
abstract: The purpose of this study was to predict the stability of imipenem in a mixed infusion. The hydrolysis of imipenem in aqueous solution was found to be accelerated by pH, and by increasing concentrations of sodium bisulfite (SBS) and L-cysteine. Equations were derived for the degradation rate constants (k(obs)) of pH, SBS and L-cysteine and fractional rate constants were estimated by nonlinear least-squares method (quasi-Newton method using the solver in Microsoft Excel) at 25°C. The activation energy (Ea) and frequency factor (A) were calculated using the Arrhenius equation. The pH of the mixed infusion was estimated using the pH characteristic (PHC) curve. From these results, an equation was derived giving the residual ratio (%) of imipenem at any time after mixing an infusion containing SBS and/or L-cysteine at any temperature and at pH 4.0-10.0. A high correlation was shown to exist between the estimated and determined residual ratios (%).
authors.affiliation: School of Pharmaceutical Science, Mukogawa Women's University, 11-68 Koshien 9-Bancho, Nishinomiya 663-8179, Japan.
authors.forename: Miyako
authors.initials: M
authors.lastname: Yoshida
authors.forename: Yuko
authors.initials: Y
authors.lastname: Takasu
authors.forename: Kaori
authors.initials: K
authors.lastname: Shimizu
authors.forename: Keiichi
authors.initials: K
authors.lastname: Asahara
authors.forename: Takahiro
authors.initials: T
authors.lastname: Uchida
mesh_terms: D061605:Administration, Intravenous; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000737:chemistry*; D003545:Cysteine / Q000737:chemistry; D004355:Drug Stability; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D015378:Imipenem / Q000008:administration & dosage / Q000737:chemistry*; D008956:Models, Chemical; D013447:Sulfites / Q000737:chemistry; D013816:Thermodynamics
chemical_list: D000900:Anti-Bacterial Agents; D013447:Sulfites; D015378:Imipenem; D003545:Cysteine; C009279:sodium bisulfite