Stability of octreotide acetate decreases in a sodium bisulfate concentration-dependent manner: compatibility study with morphine and metoclopramide injections.

PURPOSE: 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.

Hepatic steatosis rather than visceral adiposity is more closely associated with insulin resistance in the early stage of obesity.

The aim of the present study was to investigate the specific relationship between hepatic steatosis and insulin resistance in the early stage of obesity. Among general health examinees who received an ultrasound scanning, 131 subjects without fatty liver (non-FL group) and 142 subjects with fatty liver (FL group) were selected so that both groups were matched for age, sex, body mass index, and % body fat. The FL group was then subdivided into 2 groups according to the severity of steatosis by ultrasound. Insulin resistance was assessed by homeostasis model assessment for insulin resistance, serum high-molecular-weight (HMW) adiponectin, and insulin-like growth factor binding protein 1 concentrations. Unexpectedly, the non-FL group showed higher waist circumference than the FL group. Nevertheless, homeostasis model assessment for insulin resistance as well as conventional insulin resistance indexes such as serum insulin, free fatty acid, and triglyceride levels demonstrated a stepwise increase, and HMW adiponectin and insulin-like growth factor binding protein 1 demonstrated a stepwise decrease with increasing degree of hepatic steatosis. Overall, insulin resistance markers correlated with obesity indexes, but only HMW adiponectin no longer showed any meaningful correlation in the presence of fatty liver. The prevalence of BP, fasting serum glucose, and high-density lipoprotein cholesterol above or below cutoff points and subjects having 2 or more metabolic syndrome components were higher in the moderate to severe FL group compared to the non-FL group. In conclusion, these results in nondiabetic and relatively normal-body mass index subjects suggest that hepatic steatosis is independently associated with insulin resistance regardless of extrahepatic adiposity and might be the earliest event in pathogenesis of the metabolic syndrome.