Significant impairment of high-dose methotrexate clearance following vancomycin administration in the absence of overt renal impairment

摘要: Abstract Background Methotrexate is an antimetabolite cytotoxic drug which predominantly renally excreted. Vancomycin, a glycopeptide antibiotic that used in the febrile neutropaenic patient, can be nephrotoxic. There are no previous reports of any interactions between these two drugs. Patients and methods We describe patients with osteosarcoma treated high-dose methotrexate-containing chemotherapy who had significantly delayed methotrexate clearance several weeks following exposure to vancomycin. Results These were alternating consisting 12 g/m2 methotrexate, 60 mg/m2 cisplatin, 75 adriamycin 15 ifosfamide. In both patients, serum levels fell below 0.2 µmol/l within 48–96 h during initial treatment cycles. However, recent therapeutic vancomycin preceding 10 days absence overt renal impairment, manifested markedly prolonged clearance, requiring 170–231 reach ofless than µM. Subclinical impairment was documented by impaired glomerular filtration rates cases technetium 99 m diethylene triamine penta-acetic acid scanning. Subsequent cycles using unmodified schedule cleared 72 h. Both their rate re-assessed, showed marked improvement. Conclusions Recent vancomycin, even may adversely affect excretion, subsequently lead increased toxicity antimetabolite. The should measured such so appropriate dose modification made.