title: Pharmacokinetics, tissue distribution, and plasma protein binding study of platinum originating from dicycloplatin, a novel antitumor supramolecule, in rats and dogs by ICP-MS.
abstract: Dicycloplatin, as a new antitumor supramolecule, was considered to have higher solubility and higher stability compared with carboplatin. The aim of the present study was to evaluate the pharmacokinetic characteristics of platinum originating from dicycloplatin. A rapid, sensitive, and specific method with inductively coupled plasma mass spectrometry (ICP-MS) has been developed for the determination of platinum in bio-samples. The study was performed in male rats and dogs at a single dose of 10 and 5 mg kg(-1) separately by intravenous injection. Pharmacokinetic parameters were calculated by non-compartmental method, and the dose of platinum was used in the calculation of these parameters. Results showed that plasma concentrations of platinum began to decrease rapidly initially but decline slowly with a long terminal phase. The mean half-life was 27.39 and 100.98 and clearance was 0.77 and 0.08 L/h/kg for rats and dogs separately. Tissue distribution showed that platinum originating from dicycloplatin had a certain distribution in testis and prostate. Plasma protein binding proportion of platinum was increased with time. In conclusion, this research investigated the pharmacokinetic characteristics including plasma kinetics, tissue distribution, and plasma protein binding of platinum originating from dicycloplatin in rats and dogs in detail for the first time by ICP-MS.
authors.affiliation: Center of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009, Jiangsu, People's Republic of China.
authors.forename: Di
authors.initials: D
authors.lastname: Zhao
authors.forename: Yongjie
authors.initials: Y
authors.lastname: Zhang
authors.forename: Chunxiang
authors.initials: C
authors.lastname: Xu
authors.forename: Can
authors.initials: C
authors.lastname: Dong
authors.forename: Hui
authors.initials: H
authors.lastname: Lin
authors.forename: Lingli
authors.initials: L
authors.lastname: Zhang
authors.forename: Cuiyun
authors.initials: C
authors.lastname: Li
authors.forename: Shuangxia
authors.initials: S
authors.lastname: Ren
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.forename: Shuoye
authors.initials: S
authors.lastname: Yang
authors.forename: Deen
authors.initials: D
authors.lastname: Han
authors.forename: Xijing
authors.initials: X
authors.lastname: Chen
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D016190:Carboplatin / Q000494:pharmacology; D004285:Dogs; D004338:Drug Combinations; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D005971:Glutamates / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006207:Half-Life; D007275:Injections, Intravenous; D008297:Male; D013058:Mass Spectrometry / Q000379:methods*; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics*; D010984:Platinum / Q000097:blood / Q000493:pharmacokinetics*; D011467:Prostate / Q000378:metabolism; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley; D012680:Sensitivity and Specificity; D013737:Testis / Q000378:metabolism; D013997:Time Factors; D014018:Tissue Distribution
chemical_list: D000970:Antineoplastic Agents; D004338:Drug Combinations; D005971:Glutamates; D009944:Organoplatinum Compounds; C580746:diammine(1,1-cyclobutanedicarboxylate)platinum(II); C055928:cycloplatam; D010984:Platinum; D016190:Carboplatin