title: Stability of octreotide acetate decreases in a sodium bisulfate concentration-dependent manner: compatibility study with morphine and metoclopramide injections.
abstract: OBJECTIVE
  Sodium bisulfate is known to affect the stability of octreotide. However, the critical concentration of sodium bisulfate is not known. Therefore, we assessed the critical concentration of sodium bisulfate needed to preserve the stability of octreotide using actual drugs containing sodium bisulfate.
  
  
  METHODS
  Although morphine and metoclopramide preparations are considered to be compatible with octreotide, some of their products are known to contain sodium bisulfate. Thus, octreotide was mixed with preparations of sodium bisulfate solutions at serial concentrations and morphine and metoclopramide preparations containing sodium bisulfate, and octreotide stability was then evaluated using high performance liquid chromatography.
  
  
  RESULTS
  Octreotide concentrations decreased significantly at a sodium bisulfate concentration of 0.1 mg/mL or higher after 10 days when octreotide was mixed with sodium bisulfate solutions at various concentrations. A significant decrease in octreotide concentrations also occurred when it was mixed with morphine and metoclopramide preparations containing sodium bisulfate and stored for 10 days; however, slight decreases were observed in the mixture with both preparations and were within the clinically acceptable range for morphine preparations.
  
  
  CONCLUSIONS
  These results indicate that the residual rate of octreotide decreases with time in a sodium bisulfate concentration-dependent manner when octreotide was mixed with morphine or metoclopramide. However, this incompatibility may be clinically acceptable when the final sodium bisulfate concentration is lower than 0.1 mg/mL and the mixed solution is used within 7 days.
authors.affiliation: Department of Pharmaceutical Therapy & Neuropharmacology, Faculty of Pharmaceutical Sciences , Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama , Toyama , Japan ; Department of Medical Oncology , Toyama University Hospital , Toyama , Japan.
authors.forename: Kouichi
authors.identifier: 0000-0003-3875-5380
authors.initials: K
authors.lastname: Tanabe
authors.affiliation: Department of Pharmaceutical Therapy & Neuropharmacology, Faculty of Pharmaceutical Sciences , Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama , Toyama , Japan.
authors.forename: Junko
authors.initials: J
authors.lastname: Wada
authors.affiliation: Department of Pharmacy , Saiseikai Takaoka Hospital , Takaoka , Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Ohkubo
authors.affiliation: Department of Pharmaceutical Therapy & Neuropharmacology, Faculty of Pharmaceutical Sciences , Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama , Toyama , Japan.
authors.forename: Atsumi
authors.initials: A
authors.lastname: Nitta
authors.affiliation: Department of Pharmacy , Saiseikai Takaoka Hospital , Takaoka , Japan.
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Ikezaki
authors.affiliation: Department of Pharmacy , Saiseikai Takaoka Hospital , Takaoka , Japan.
authors.forename: Miyako
authors.initials: M
authors.lastname: Takeuchi
authors.affiliation: Department of Pharmacy , Saiseikai Takaoka Hospital , Takaoka , Japan.
authors.forename: Aya
authors.initials: A
authors.lastname: Handa
authors.affiliation: Department of Pharmacy , Saiseikai Takaoka Hospital , Takaoka , Japan.
authors.forename: Mai
authors.initials: M
authors.lastname: Tanaka
authors.affiliation: Department of General and Digestive Surgery , Himi Municipal Hospital of Kanazawa Medical University , Kanazawa , Japan.
authors.forename: Nozomu
authors.initials: N
authors.lastname: Murakami
authors.affiliation: Department of Medical Oncology , Toyama University Hospital , Toyama , Japan.
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Kashii
authors.affiliation: Department of Pharmacy , Saiseikai Takaoka Hospital , Takaoka , Japan.
authors.forename: Hidenori
authors.initials: H
authors.lastname: Kitazawa
keywords: PALLIATIVE CARE; compatibility; metoclopramide; morphine; sodium bisulfate