Niigata University of Pharmacy & Applied Life Sciences

In clinical practice, it is sometimes necessary to administer the thrombin inhibitor dabigatran etexilate (DE) to patients who have difficulty taking medications by mouth, but little is known about the pharmacokinetics and plasma concentrations of DE when it is administered via gavage. We describe a case in which it was necessary to orally administer the decapsulated contents of DE capsules.

A 79-year-old man with atrial fibrillation, quadriplegia, and a history of liver dysfunction who had difficulty swallowing was administered DE via a nasogastric tube while monitoring his plasma dabigatran concentration. To prepare the DE for administration, the contents of DE capsules were suspended in water. Despite administering only half the standard dose, the patient’s blood dabigatran concentrations were comparable to those of patients receiving a full dose, potentially due to improved solubility and dispersion in the gastrointestinal tract after decapsulation. Coagulation status, as measured by activated partial thromboplastin time (aPTT), remained within safe limits, with no significant bleeding. DE was administered via a nasogastric tube for 8 days with monitoring.

This case suggests that, for patients who cannot take medication orally, DE can be administered safely via a nasogastric tube at lower doses while closely monitoring blood drug concentrations and aPTT levels. Further research is needed to explore the pharmacokinetics and understand the impact of diet on the absorption of DE administered via nasogastric tube. This administration method may broaden treatment options for atrial fibrillation in patients with difficulty in oral intake.

Macrophage polarization plays a critical role in cancer immunotherapy. This study aimed to evaluate the synergistic effects of 3-(trihydroxygermyl)propanoic acid (THGP), an organogermanium compound, and the immunostimulant lipopolysaccharide (LPS) derived from Pantoea agglomerans on M1 macrophage differentiation and antitumor activity.

RAW 264.7 cells were treated with THGP, LPS, or their combination for 1, 4, or 10 days. Morphological changes, M1 marker (CD80 and CD86) expression, cytokine production (IL-1β and IL-6), phagocytic activity, and cytotoxicity against B16-F10 melanoma cells were assessed using microscopy, qPCR, western blotting, immunofluorescence staining, and luciferase assays.

After one day of treatment, LPS treatment, both alone or in combination with THGP, increased M1 marker expression. By day 4, both agents individually induced M1 differentiation; their combination had a synergistic effect on cytokine production and phagocytic activity. Antitumor effects were observed only with the combined treatment. After 10 days, single and combined treatments resulted in comparable phagocytic and antitumor activities.

The combination of THGP and LPS synergistically promotes M1 macrophage differentiation and enhances phagocytic and antitumor activities through distinct mechanisms. These findings suggest potential applications of this combination in cancer immunotherapy.

Boron neutron capture therapy (BNCT) is a novel treatment that induces targeted tumor cell damage through the selective accumulation of ¹⁰B compounds in cancer cells followed by the production of alpha and lithium particles using thermal neutron irradiation. Despite its potential, clinical applications of BNCT for recurrent gastrointestinal cancers remain limited. This study presents the first pilot clinical evaluation of BNCT using intravenous boronophenylalanine (¹⁰BPA) for such cancers.

Four patients with recurrent gastrointestinal cancers were enrolled in this phase I-II clinical study. All had tumors refractory to standard treatments, including surgery, chemotherapy, and radiotherapy. BNCT was performed using thermal neutron irradiation at Kyoto University Research Reactor. ¹⁰BPA was administered intravenously at 400 mg/kg, and no severe adverse effects were observed. Tumor responses varied, with one patient achieving partial response and three demonstrating stable disease at three months post-treatment. Notably, BNCT alleviated cancer-related symptoms, such as pain and nerve compression, improving patients' quality of life. Dosimetric evaluations confirmed effective tumor doses with acceptable exposure to surrounding normal tissues.

BNCT is a promising modality for recurrent gastrointestinal cancers, offering symptom relief and potential antitumor effects. Its safety and feasibility were demonstrated in this study. Future research should explore fractionated BNCT and combination therapies with immunotherapy or targeted agents to enhance efficacy further.