Pharmacokinetics of methotrexate in continuous ambulatory peritoneal dialysis

The pharmacokinetics of methotrexate and its 7-hydroxy metabolite were studied in a patient undergoing continuous ambulatory peritoneal dialysis. A biphasic plasma-disappearance pattern of methotrexate was observed, with half-lives of 3.5 and 29 hours. The 7-hydroxy metabolite accumulated and showed a very slow rate of elimination, with an estimated final elimination half-life of over 120 hours. The mean peritoneal clearance rate of methotrexate was 0.13 l/h (range 0.05-0.20 l/h), dwell times significantly influenced the clearance rate. Strict monitoring of the methotrexate level, even after low doses, is necessary in continuous ambulatory peritoneal dialysis patients, to prevent serious bone marrow toxicity.