Pharmacokinetics of the cis-platin analog ethylenediaminemalonatoplatinum(II) (JM-40) was studied in 28 cycles of 19 patients during the phase I study of this drug. The drug was administered intravenously by short-term (10-60min) infusion. Doses ranged from 20 to 1, 200 mg m‑2. JM-40 was determined in plasma ultrafiltrate and urine by HPLC. Platinum (Pt) concentrations were determined in plasma, plasma ultrafiltrate, urine and red blood cells by atomic absorption spectrometry up to 5 days after administration of the drug. Ultrafilterable Pt could be determined up to 45 days after the infusion in one patient sampled over such a long period. Pharmacokinetics of JM-40 showed a linear behaviour. The final half-life of total Pt in plasma was 4.1 +0.9 days. The disposition of JM-40 was similar to that of ultrafilterable Pt in respect to t½ α, (10 and 13 min), t½ β (44 and 57 min), volumes of distribution Vc (11 and 121) and Vss (17 and 201), systemic clearance (256 and 223ml min‑1), renal clearance (69 and 73 ml min‑1) and metabolic clearance (183 and 154ml min-1). During the first 6h 27±9% of the administered dose was excreted as JM-40. Cumulative platinum excretion in the urine amounted to 29±13%, 42±14% and 60±13% over the first 6h, 24h and 5 days, respectively. The uptake of platinum in red blood cells was limited, comprising only 0.24±0.12% of the administered dose. Although JM-40 and carboplatin are structurally closely related, pharmocokinetics and toxicity of JM-40 were more similar to cis-platin than to carboplatin.
ASJC Scopus subject areas
- Cancer Research