Possible Interaction: Albumin and Methotrexate

“The considerable discrepancy in the molecular weight of MTX (454 Da) and albumin (about 67 000 Da) tempted researchers to load multiple drug molecules on one carrier molecule.”

“Increased MTX concentration were paralleled by significantly increased albumin concentrations in the CSF.”

“Background:Although methotrexate is highly bound to albumin , it is thought to be removed by hemodialysis and not by peritoneal dialysis.”

“Drugs used in combination with MTX in therapy (vincristine, vinblastine, cyclophosphamide, 5-fluorouracil, prednisone) depress the MTX binding to albumins.”

“ MTX binds to two kinds of albumins binding sites, with different binding constants: K1 = 8.88 mM-1 and K2 = 1.76 mM-1.”

“ MTX induced significant increase in circulating liver function marker enzymes and bilirubin with concomitant declined albumin levels.”

“Lactosylation of albumin conjugates further enhanced the delivery of MTX to the liver in a lactose content-dependent manner, accompanied by decreased accumulation of MTX in the lung and heart as well as kidney.”

“Taken together, the pharmacokinetics and liver targetability of MTX could be favorably modulated by controlling the lactose content on the albumin conjugates.”

“The total MTX level accumulated in the liver was 2.9-, 4.1-, and 11.0-fold higher at 1 h and 5.4-, 7.0-, and 16.5-fold higher at 4 h after injection of MTX-L0, L5, L24 albumin conjugates compared with MTX alone.”

“Additive effects were observed for a combination of MTX‐albumin and MTX.”

“In addition the conjugation to albumin might enhance the therapeutic effects over those achieved by long-term continuous infusion of MTX , as MTX(1)-RSA enters the cells by a different uptake mechanism.”

“The presence of albumin in the buffer markedly reduces bromosulfophthalein inhibition of MTX influx, but has a much lesser effect on taurocholate inhibition of methotrexate influx, presumably related to the much higher affinity of albumin for bromosulfophthalein than for taurocholate.”

“This report is concerned with the alteration in biochemical and pharmacologic properties of amethopterin (Methotrexate) (MTX) when it is covalently attached to albumin.”