Pharmacokinetics of a novel anticancer ruthenium complex (KP1019, FFC14A) in a phase I dose-escalation study.
A phase I and pharmacokinetic study was carried out with the new ruthenium complex indazolium trans-[tetrachlorobis(1H-indazole)ruthenate(III)] (KP1019, FFC14A). Seven patients with various types of solid tumours refractory to standard therapy were treated with escalating doses of KP1019 (25-600 mg) twice weekly for 3 weeks. No dose-limiting toxicity occurred. Ruthenium plasma concentration-time profiles after the first dose and under multiple-dose conditions were analysed using a compartmental approach. The pharmacokinetic disposition was characterised by a small volume of distribution, low clearance and long half-life. Only a small fraction of ruthenium was excreted renally. The area under the curve values increased proportionally with dose indicating linear pharmacokinetics.
Lentz
Frederike
F
Department of Clinical Pharmacy, Institute of Pharmacy, University of Bonn, An der Immenburg 4, Bonn, Germany.
Drescher
Anne
A
Lindauer
Andreas
A
Henke
Magdalena
M
Hilger
Ralf A
RA
Hartinger
Christian G
CG
Scheulen
Max E
ME
Dittrich
Christian
C
Keppler
Bernhard K
BK
Jaehde
Ulrich
U
D000328:Adult; D000368:Aged; D000465:Algorithms; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D019540:Area Under Curve; D005260:Female; D006801:Humans; D007191:Indazoles / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D009369:Neoplasms / Q000188:drug therapy*; D009942:Organometallic Compounds; D017975:Ruthenium Compounds / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*
D000970:Antineoplastic Agents; D007191:Indazoles; D009942:Organometallic Compounds; D017975:Ruthenium Compounds; C499292:indazolium trans-(tetrachlorobis(1H-indazole)ruthenate (III))