Pharmacokinetics of a new antitumor 3-arylisoquinoline derivative, CWJ-a-5.
1-(4-Methylpiperazinyl)-3-phenylisoquinoline hydrochloride (CWJ-a-5) is a newly developed from benzo[c]phenanthridine alkaloids and derivative and has exhibited potent antitumor activities, in vitro and in vivo. The pharmacokinetics of this novel antitumor 3-arylisoquinoline derivative was studied after intravenous (i.v.), oral (p.o.) and hepatoportal (p.v.) administration in rats. A simple high performance liquid chromatographic method was developed to determine the concentrations of CWJ-a-5 in plasma, bile and urine. Plasma concentration profiles of CWJ-a-5 were best fitted by the two-compartment model after i.v. administration and showed a linear pharmacokinetic behavior up to 20 mg/kg doses. The half-life of CWJ-a-5 in the post-distributive phase (t1/2beta), total-body plasma clearance (CLt), and volume of distribution at steady-state (Vdss) were 86.9 min, 5.72 l/h per kilogram and 9.79 l/kg, respectively, after i.v. administration of 10 mg/kg. Biliary and urinary excretion of CWJ-a-5 was < 1% after i.v. injection of 10 mg/kg. The bioavailability of CWJ-a-5 after p.o. and p.v. administration (50 and 10 mg/kg, respectively) was 52.9 and 72.2%, respectively. Gastrointestinal bioavailability was calculated to be 73.3%. The apparent partition coefficient (log P) of CWJ-a-5 between n-octanol and water was 2.64. Plasma protein binding of CWJ-a-5 measured by the ultrafiltration method was > 95%.
Kim
K E
KE
College of Pharmacy, Pusan National University, 609735, Pusan, South Korea.
Cho
W J
WJ
Chang
S J
SJ
Yong
C S
CS
Lee
C H
CH
Kim
D D
DD
D000818:Animals; D000970:Antineoplastic Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D019540:Area Under Curve; D001646:Bile / Q000378:metabolism*; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D007546:Isoquinolines / Q000493:pharmacokinetics; D008297:Male; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility
D000970:Antineoplastic Agents; C428783:CWJ-a-5; D007546:Isoquinolines