Pharmacokinetics ofcis-dichloro-trans-dihydroxy-bis-isopropylamine platinum IV (iproplatinum, chip) in patients with normal and impaired renal function and following intraperitoneal administration
- 16 Downloads
CHIP is a quadrivalent platinum (Pt) complex, introduced clinically as a less toxic alternative tocis-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 and51Cr-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.
Key wordsCHIP pharmacokinetics Intraperitoneal
Unable to display preview. Download preview PDF.
- 1.Highby D J, Wallace H J Jr, Alberts D, Holland J F: Diamminedichloro platinum in the chemotherapy of testicular tumours.J Urol 112, 110 (1971).Google Scholar
- 2.Wiltshaw E, Carr T:Cis-platinum(II) diamminedichloride clinical experiences of the Royal Marsden Hospital and Institute of Cancer Research.Recent Results Cancer Res 48, 178 (1974).Google Scholar
- 5.Pendyala L, Greco W, Cowens J W, Madajewicz S, Creaven P J: Pharmacokinetics of CHIP in patients with advanced cancer.Cancer Chemother Pharmac 11, 23 (1983).Google Scholar
- 6.Pendyala L., Madajewicz S., Lele S B, Arbuck S G, Creaven P J: Evaluation of the nephrotoxicity of iproplatin (CHIP) in comparison to cisplatin by the measurement of urinary enzymes.Cancer Chemother Pharmac 15, 203 (1985).Google Scholar
- 11.Ozols R, Locker G, Doroshow J: Pharmacokinetics of adriamycin and tissue penetration in murine ovarian cancer.Cancer Res 29, 3209 (1979).Google Scholar
- 14.Chantier C, Garnett E S, Parsons V, Veall N: Glomerular filtration rate measurement in man by the single injection method using5lCr-EDTA.Clin Sci 37, 169 (1969).Google Scholar
- 16.Bevington P R:Data Reduction and Error Analysis for the Physical Sciences, pp. 235–236. New York, McGraw-Hill (1969).Google Scholar
- 17.Gormley P E, Bull J M, LeRoy A F, Cysyk R: Kinetics of cis-dichlorodiammine platinum.Clin Pharmac Ther 25, 351 (1979).Google Scholar
- 18.Speyer J L, Myers C E: The use of peritoneal dialysis for delivery of chemotherapy to intraperitoneal malignancies.Recent Res Cancer Res 74, 164 (1980).Google Scholar