ABSTRACT
WHAT IS KNOWN AND OBJECTIVE: Methotrexate (MTX) is an important agent for the treatment of primary central nervous system lymphomas (PCNSL) but needs to be given in big doses by intravenous infusions to achieve therapeutic concentrations in the cerebrospinal fluid. However, co-administration with many drugs may delay the excretion of MTX which may cause serious adverse effects if the serum concentration exceeds 0.1 µmol/L 72 h after an intravenous infusion. CASE SUMMARY: A 67-year-old Japanese female with PCNSL was treated with high-dose MTX-based chemotherapy. The serum MTX concentration 72 h post-infusion was 0.153 µmol/L when she was taking levofloxacin (LVFX) but <0.1 µmol/L 72 h after 4 subsequent infusions when she was not taking LVFX. She was given many other drugs but the timing of the short course of LVFX and the fact that ciprofloxacin also delays MTX excretion suggests that LVFX was the cause. WHAT IS NEW AND CONCLUSION: Co-administration of LVFX may delay the excretion of MTX. Therefore, serum concentrations of MTX should be monitored to help prevent and improve the management of potentially serious MTX drug-drug interaction.
Subject(s)
Anti-Bacterial Agents/pharmacology , Antimetabolites, Antineoplastic/pharmacokinetics , Central Nervous System Neoplasms/drug therapy , Levofloxacin/pharmacology , Lymphoma/drug therapy , Methotrexate/pharmacokinetics , Aged , Antimetabolites, Antineoplastic/administration & dosage , Antimetabolites, Antineoplastic/blood , Antimetabolites, Antineoplastic/therapeutic use , Dose-Response Relationship, Drug , Drug Interactions , Female , Humans , Methotrexate/administration & dosage , Methotrexate/blood , Methotrexate/therapeutic useABSTRACT
WHAT IS KNOWN AND OBJECTIVE: Multi-drug combinations often make chemotherapy difficult owing to drug-drug interactions (DDIs). We report a rare and difficult-to-treat case due to DDIs between drugs for Mycobacterium avium complex (MAC) infection and antiepileptic drugs. CASE DESCRIPTION: A 70-year-old Japanese woman was diagnosed as having pulmonary MAC disease. She had a history of symptomatic epilepsy, which was successfully treated with phenytoin and phenobarbital. Serum phenytoin concentrations increased upon the initiation of MAC infection treatment. WHAT IS NEW AND CONCLUSION: We evaluated DDIs and adjusted the dosage of drugs by monitoring the serum drug level.
Subject(s)
Anti-Bacterial Agents/pharmacology , Anticonvulsants/pharmacokinetics , Phenytoin/pharmacokinetics , Aged , Anti-Bacterial Agents/administration & dosage , Anticonvulsants/administration & dosage , Dose-Response Relationship, Drug , Drug Interactions , Epilepsy/drug therapy , Female , Humans , Mycobacterium avium Complex/isolation & purification , Mycobacterium avium-intracellulare Infection/drug therapy , Phenobarbital/administration & dosage , Phenytoin/administration & dosageABSTRACT
Sofalcone, 2'-carboxymethoxy-4,4'-bis(3-methyl-2-butenyloxy)chalcone, has been used as an anti-ulcer agent, although its precise molecular mechanism has not been completely understood. In the current study, we tested the effects of sofalcone on the inflammatory crosstalk between macrophages and adipocytes and on the differentiation of pre-adipocytes. We found that sofalcone has a strong suppressive effect on the production of nitric oxide (NO), tumor necrosis factor (TNF)alpha, and monocyte chemoattractant protein (MCP)-1 in the culture medium of a coculture system containing RAW264.7 macrophages and 3T3-F442A adipocytes stimulated with lipopolysaccharide (LPS). The suppressive effect of sofalcone on NO production was attenuated by treatment with tin-protoporphyrin (SnPP), a heme-oxygenase (HO)-1 inhibitor. Western blotting analysis showed that sofalcone increased HO-1 expression in both 3T3-F442A mature adipocytes and undifferentiated fibroblasts. Sofalcone also inhibited the differentiation of 3T3-F442A pre-adipocytes into adipocytes, which was restored by SnPP treatment. These results suggest that sofalcone has preferable properties for obesity or metabolic syndrome.
