Pharmacokinetics of cis-dichloro-trans-dihydroxy-bis-isopropylamine platinum IV (iproplatinum, CHIP) in patients with normal and impaired renal function and following intraperitoneal administration.
CHIP is a quadrivalent platinum (Pt) complex, introduced clinically as a less toxic alternative to cis-platinum. The drug's major route of excretion is via the kidneys, and in this study the pharmacokinetics of unchanged CHIP, filterable Pt and total Pt have been determined following intravenous administration to patients with a range of renal function. Total Pt and filterable Pt in plasma decayed biexponentially and was fitted to a two-compartment model, whereas unchanged CHIP declined monoexponentially and was best fitted to a one-compartment model, according to Akaike's information criteria. There is a correlation between the unchanged CHIP clearance and 51Cr-EDTA clearance. The pharmacokinetics of CHIP was determined following intraperitoneal (i.p.) administration (dose, 150-300 mg m-2 4 h dwell time) and a regional advantage (peritoneal peak concentration/plasma peak concentration) of approximately 30 fold was seen. It is likely that the dose of CHIP will need to be reduced in patients with impaired renal function, and the use of i.p. CHIP in ovarian carcinoma warrants further study.
Kerr
D J
DJ
University Department of Medical Oncology, Glasgow University.
Harding
M
M
Farmer
J G
JG
Amarin
J
J
Blackie
R G
RG
Harland
S J
SJ
Kaye
S B
SB
D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007263:Infusions, Parenteral; D007674:Kidney Diseases / Q000097:blood / Q000378:metabolism*; D008657:Metabolic Clearance Rate; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D010051:Ovarian Neoplasms / Q000097:blood / Q000188:drug therapy; D010529:Peritoneal Cavity / Q000378:metabolism; D010984:Platinum / Q000493:pharmacokinetics
D009944:Organoplatinum Compounds; D010984:Platinum; C023359:iproplatin