Calcium Levofolinate

Calcium Levofolinate is the calcium salt of Levoleucovorin, which is the enantiomerically active form of folinic acid.

Effect of freeze-thawing on the long-term stability of calcium levofolinate in 5% dextrose stored on polyolefin infusion bags.[Pubmed:19583675]

J Clin Pharm Ther. 2009 Aug;34(4):423-8.

BACKGROUND: Calcium Levofolinate infusions could be prepared in advance by a centralized intravenous additive service (CIVAS) to improve safety and time management. OBJECTIVE: To investigate the effect of freezing, microwave thawing and long-term storage at 5 +/- 3 degrees C on the stability of Calcium Levofolinate in 5% dextrose solution. METHODS: Solutions of 250 mL of 5% dextrose in polyolefin bags (n = 5) containing approximately 400 mg of Calcium Levofolinate were prepared under aseptic conditions and frozen for 95 days at -20 degrees C. The solutions were then thawed using microwaves and stored at 5 +/- 3 degrees C for 1 month. The Calcium Levofolinate concentrations were measured by high performance liquid chromatography (HPLC). Visual inspection was performed and pH was measured periodically during the storage at 5 +/- 3 degrees C. Stability of the solution was defined as a concentration remaining superior to 90% of the initial concentration by regression analysis as recommended by the Food and Drug Administration (FDA). RESULTS: No colour change or precipitation in the solutions was observed. Calcium Levofolinate infusions were stable when stored at 5 +/- 3 degrees C during 1 month after freeze-thaw treatment. Throughout this period, the lower confidence limit of the estimated regression line of concentration-time profile remained above 90% of the initial concentration. Slight change in pH values from 6.52 +/- 0.01 to 6.50 +/- 0.01 during storage time did not affect retention time on HPLC and has no clinical consequence, the solutions remaining in the acceptable range for perfusion (4 Calcium Levofolinate in 5% dextrose infusion may be prepared, frozen in advance by CIVAS, and then microwave thawed before use. Such treatment extends long-term stability and releases pharmacist's time for major activities such as checking medication order errors.

[A case of gastric cancer with multiple liver metastases responding to combined hepatic arterial and aortic infusion chemotherapy with cisplatinum, 5-fluorouracil, and levofolinate calcium].[Pubmed:12402439]

Gan To Kagaku Ryoho. 2002 Oct;29(10):1835-9.

A 64-year-old man who had type IIc-like advanced gastric cancer with multiple liver metastases was admitted to our hospital. He underwent combined hepatic arterial and aortic infusion chemotherapy with cisplatinum (CDDP), 5-fluorouracil (5-FU), and levofolinate calcium (l-LV). After 4 weeks (2 courses) of chemotherapy, a partial response was achieved for the hepatic metastasis. Therefore, distal gastrectomy, right hepatectomy combined with caudate lobectomy, partial resection of the hepatic right lobe, and microwave coagulation therapy of the residual tumor of the hepatic right lobe were performed. With this operation, all tumor cells were removed or killed. Histopathologically, almost all of the primary tumor was fibrous tissue, and only a few sections of moderately differentiated adenocarcinoma observed in the subserosal layer. In the periphery of the metastatic lesion, residual well to moderately differentiated adenocarcinomas were observed, and in the center, only necrotic tissue was seen. The postoperative course was uneventful. Now, one year and seven months after the operation, he is followed as an outpatient. Combined hepatic arterial and aortic infusion chemotherapy with CDDP, 5-FU, and l-LV is thought to be an effective regimen for advanced gastric cancer with multiple liver metastases.

Development and validation of a robust capillary electrophoresis method for impurity profiling of calcium levofolinate including the (6R,2'S)-diastereomer using statistical experimental design.[Pubmed:14981706]

Electrophoresis. 2004 Feb;25(4-5):766-77.

A chiral capillary electrophoresis assay for the simultaneous determination of the optical purity and of related substances of Calcium Levofolinate has been developed and validated. Using 2,6-dimethyl-beta-cyclodextrin as chiral selector at a concentration of 20 mg/mL, the method was optimized using a full factorial design with four factors including pH and concentration of the background electrolyte, column temperature and separation voltage. Optimized conditions were a 40 mM sodium tetraborate buffer, pH 9.9, a capillary temperature of 16 degrees C, and an applied voltage of 21 kV. Methotrexate was used as internal standard to compensate for injection errors and fluctuations of the migration times. A multiple linear regression model was also used to test the robustness of the method. Validation was performed with respect to specificity, linearity, range, limit of quantification and detection, precision, and accuracy. The assay allowed the detection and determination of related substances including the diastereomeric (6R,2'S)-impurity of levofolinic acid at the 0.1% level, the identification threshold of impurities for orally administered drugs for human use defined by the International Conference on Harmonization guidelines as well as the European Pharmacopoeia.

[Successful treatment of an elderly patient with advanced gastric cancer using low-doses of 5-fluorouracil, levofolinate calcium, and cis-platinum with chronomodulation].[Pubmed:17108731]

Gan To Kagaku Ryoho. 2006 Nov;33(11):1633-6.

An 83-year-old man was admitted to our hospital for abdominal pain and severe vomiting. Gastrography and gastric endoscopy revealed that the pylorus was obstructed by a giant type 2 cancer in the lower gastric body. Furthermore, computed tomography revealed multiple metastases in the para-aortic lymph nodes. The man was unable to consume any food or liquid, and could not take medicine orally. Paclitaxel was not effective in treating the lymph node metastases or vomiting; therefore a chronomodulated schedule was used, which involved the administration of low doses of 5-fluorouracil, levofolinate calcium and cis-platinum (FLP) each night. After four cycles of low-dose FLP therapy, the patient was able to consume food orally. The patient has partially responded to this regime over five months. In the current study, low-dose FLP therapy with chronomodulation was considered an effective treatment, and there were no severe adverse side effects. This case suggested that low-dose FLP therapy with chronomodulation is promising for the treatment of gastric cancer in elderly patients who can not take medicine orally, and further trials are warranted.