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Pharmacokinetics of cisplatin and methotrexate in a patient suffering from advanced ureteral tumor accompanied by chronic renal failure, undergoing combined hemodialysis and systemic M-VAC chemotherapy
Authors:Tokunaga J  Kikukawa H  Nishi K  Kitani K  Fujii J  Honda J  Wada Y  Ueda S  Nakano M
Affiliation:Dept. of Pharmaceutical Services, Kumamoto University Hospital.
Abstract:The pharmacokinetics of cisplatin and methotrexate were determined in a patient suffering from advanced ureteral tumor accompanied by chronic renal failure undergoing 4 consecutive cycles of M-VAC chemotherapy and hemodialysis. No significant difference was observed in t1/2, AUC or CLtot of total platinum between the patient with the chronic renal failure and patients with normal renal function. The AUC and CLtot of free platinum in the patient with the chronic renal failure were higher and lower, respectively, than in the patients with normal renal function. The free cisplatin rebounded remarkably after the end of dialysis, which may be partly attributed to an increase in the AUC and decrease in CLtot. However, the dialysis index was about 75 and 85% in the 3rd and 4th cycles, respectively. The t1/2 and CLtot of methotrexate in the patient with the chronic renal failure tended to be longer and smaller than those in patients with normal renal function, respectively. Seventy-two hours after administration, the methotrexate level was 0.02 microM, which was not at the high-risk level of high-dose therapy. After four cycles of M-VAC therapy, the rest of the right ureteral tumor was extirpated and the clinical response was CR. In conclusion, it is considered that cisplatin and methotrexate can be given to a patient with chronic renal failure. However, the cisplatin and methotrexate serum levels must be monitored, even after very low doses.
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