PHARMACOKINETICS OF ELEMENTAL PLATINUM (ULTRAFILTRATE AND TOTAL) AFTER A THIRTY MINUTE INTRAVENOUS INFUSION OF ORMAPLATIN
✍ Scribed by WILLIAM D. FIGG; MICHAELE C. CHRISTIAN; RICHARD LUSH; CHARLES J. LINK; PATRICIA DAVIS; ELISE KOHN; GISELE SAROSY; MACE L. ROTHENBERG; RAYMOND B. WEISS; NATHAN RYAN; JOAN JACOBS; EDDIE REED
- Publisher
- John Wiley and Sons
- Year
- 1997
- Tongue
- English
- Weight
- 185 KB
- Volume
- 18
- Category
- Article
- ISSN
- 0142-2782
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✦ Synopsis
Preclinical data suggest that ormaplatin (tetrachloro-(d1-trans)-1, 2-diamminocyclohexaneplatinum) has substantial activity in cisplatin-resistant tumor models and may be less nephrotoxic than cisplatin. Based on these data we initiated a phase I clinical trial in patients with refractory metastatic cancer. This report characterizes the pharmacokinetic pro®le of both the total plasma concentrations of elemental platinum and the unbound ultra®ltrate concentrations of elemental platinum, following a 30 min intravenous infusion of ormaplatin. Platinum concentrations were determined by AAS, and pharmacokinetic parameters for both the total plasma concentration and the ultra®ltrate concentration of elemental platinum were determined using both compartmental and noncompartmental methods. Twenty-eight patients (14 males and 14 females; median age, 58) received ormaplatin. There was a linear relationship between C max and dose (r 2 =0´945) and AUC and dose (r 2 =0´976). Ormaplatin is more accurately described by a two-compartment model than by a one-compartment model. The distribution half-life (t 1/2a ) was 0´3 h and the terminal half-life (t 1/2b ) was 39´1 h. The volume of the central compartment (V) was 68´6 L and the volume of distribution at steady state (V dss ) was 183 L. Like total plasma platinum, unbound platinum is also best characterized by a two-compartment model. The elimination of free platinum is also biphasic with a distribution half-life (t 1/2a ) of 0´3 h and a terminal half-life (t 1/2b ) of 19´3 h. The mean volume of the central compartment (V) was 200´5 L, and the mean volume of distribution at steady state (V dss ) was 560´5 L. Clinical development of ormaplatin has been terminated due to increased frequency of neurological complications noted over other platinum agents; however, the pharmacokinetics are, in general, similar to those of other clinically used platinum compounds. &1997 by John Wiley & Sons, Ltd.