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
Objective: Tacrolimus is administered to patients undergoing haematopoietic stem cell transplantation (HSCT) as prophylaxis for graft-versus-host disease. As a high blood tacrolimus concentration within a narrow therapeutic range must be maintained after HSCT, therapeutic drug monitoring (TDM) is necessary. We investigated the correlation between blood tacrolimus concentration and blood cell count in HSCT patients to assess how changes in blood cell count affect tacrolimus TDM. Methods: A retrospective analysis was performed for 24 patients who underwent allogeneic HSCT and received tacrolimus. The correlation between variations in blood tacrolimus concentration and blood cell count was evaluated for three consecutive weeks, starting 1 week after HSCT. Results: Variations in blood tacrolimus concentration were significantly correlated with variations in red blood cell (RBC) count, haemoglobin level and haematocrit value, but not with variations in white blood cell or platelet counts. Further, the above variations were significantly correlated in patients undergoing cord blood transplantation and peripheral blood stem cell transplantation, but not in those undergoing bone marrow transplantation. Conclusions: These findings demonstrate that RBC count is associated with variations in blood tacrolimus concentration, with the relevance of this association depending on the source of transfused stem cells. Thus, variations in RBC count might be useful for tacrolimus TDM.
