Pharmacokinetics of the prototype and hydrolyzed carboxylic forms of ginkgolides A, B, and K administered as a ginkgo diterpene lactones meglumine injection in beagle dogs.

Ginkgo diterpene lactones meglumine injection (GDLI) is a commercially available product used for neuroprotection. However, the pharmacokinetic properties of the prototypes and hydrolyzed carboxylic forms of the primary components in GDLI, i.e., ginkgolide A (GA), ginkgolide B (GB), and ginkgolide K (GK), have never been fully evaluated in beagle dogs. In this work, a simple, sensitive, and reliable method based on ultra-fast liquid chromatography-tandem mass spectrometry (UFLC-MS/MS) was developed, and the prototypes and total amounts of GA, GB, and GK were determined in beagle dog plasma. The plasma concentrations of the hydrolyzed carboxylic forms were calculated by subtracting the prototype concentrations from the total lactone concentrations. For the first time, the pharmacokinetics of GA, GB, and GK were fully assessed in three forms, i.e., the prototypes, the hydrolyzed carboxylic forms, and the total amounts, after intravenous administration of GDLI in beagle dogs. It was shown that ginkgolides primarily existed in the hydrolyzed form in plasma, and the ratio of hydrolysates to prototype forms of GA and GB decreased gradually to a homeostatic ratio. All of the three forms of the three ginkgolides showed linear exposure of AUC to the dosages. GA, GB, and GK showed a constant half-life approximately 2.7, 3.4, and 1.2 h, respectively, which were consistent for the forms at three dose levels (0.3, 1.0, and 3.0 mg·kg-1) and after a consecutive injection of GDLI for 7 days (1.0 mg·kg-1).

Clinical evaluation of oral Fructus bruceae oil combined with radiotherapy for the treatment of esophageal cancer.

OBJECTIVE: To evaluate the therapeutic efficacy and side effects of oral Fructus bruceae oil combined with radiotherapy in the treatment of esophageal cancer. METHODS: A total of 80 patients with esophageal cancer were equally and randomly divided into two groups. The patients in Group A were treated with radiotherapy (60-65 Gy, 6-7 weeks) and oral Fructus bruceae oil (20 mL, 3 times per day for 12 weeks), while the patients in Group B were treated with radiotherapy alone. The short-term effect was evaluated by Response Evaluation Criteria in Solid Tumors (RECIST) and quality of life (QOL) was evaluated by the Karnofsky scoring (KFS). The outcome measures included complete remission (CR) rate, partial remission (PR) rate, effective rate as CR+PR, patients' QOL and adverse effects. RESULTS: After 12-week treatment, the CR and CR+PR were significantly higher in Group A than those in Group B (P <0.05). There was an improvement in esophageal obstruction of 87.5% and 60.0%, respectively, and in KFS of 84.6% and 43.9%, respectively, in Groups A and B. CONCLUSION: Oral medication with oral Fructus bruceae oil could effectively improve the efficacy of radiotherapy in esophageal cancer, including a reduction in esophageal obstruction, and also reduce the side effects of radiotherapy; thus it would be very promising for clinical application.