Simultaneous observation of the metabolism of cisplatin and NAMI-A in human plasma in vitro by SEC-ICP-AES.
Single drug-based cancer therapies are frequently associated with the development of drug resistance. To overcome this problem, combination therapy with two or more anticancer drugs is a promising strategy, but clinical studies are logistically challenging and costly. Intermediary in vitro studies, however, can provide critical insight to decide whether one should proceed to in vivo studies. To this end, cisplatin and the Ru-based anticancer drug NAMI-A were added to human plasma and the size distribution of Pt-containing and Ru-containing entities was determined over a 2 h period. The results revealed a dramatically different rate of plasma protein binding for each drug and/or their hydrolysis products. Both drugs bound to the same apparent plasma proteins, but crucially they did not adversely affect each other's metabolism. Therefore, combination therapy of patients with these metallodrugs should be further assessed in clinical studies in order to systematically develop an effective combination therapy protocol to prevent the resurgence of cancer.
Department of Chemistry, University of Calgary, 2500 University Drive NW, Calgary, AB, T2N 1N4, Canada.
Melani
M
Sooriyaarachchi
Jason L
JL
Wedding
Hugh H
HH
Harris
Jürgen
J
Gailer
D002945:Cisplatin / Q000097:blood* / Q000737:chemistry / Q000378:metabolism*; D004121:Dimethyl Sulfoxide / Q000031:analogs & derivatives* / Q000097:blood / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D009942:Organometallic Compounds / Q000097:blood* / Q000737:chemistry / Q000378:metabolism*; D017975:Ruthenium Compounds; D013054:Spectrophotometry, Atomic
D009942:Organometallic Compounds; D017975:Ruthenium Compounds; C113661:imidazolium-bis(imidazole)dimethylsulfoxideimidazotetrachlororuthenate(III); D002945:Cisplatin; D004121:Dimethyl Sulfoxide