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Vol. 28, Issue 11, 1379-1384, November 2000

Early Biotransformations of Oxaliplatin after Its Intravenous Administration to Cancer Patients

Pierre Allain, Oliver Heudi, Annie Cailleux, Anne Le Bouil, Francis Larra, Michele Boisdron-Celle, and Erik Gamelin

Laboratoire de Pharmacologie et Toxicologie, Centre Hospitalier Universitaire, Angers, France (P.A., O.H., A.C., A.L.B.); and Departements d'Oncologie Médicale et de Pharmacologie Clinique, Centre Paul-Papin, Centre Regional de Lutte contre le Cancer, Angers, France (F.L., M.B.-C., E.G.)

This article deals with the fate of oxaliplatin 1 and 3 h after its i.v. administration (130 mg/m2) to three patients. Its binding to plasma proteins and penetration into red blood cells were monitored by chromatography on-line with inductively coupled plasma mass spectrometry. Oxaliplatin biotransformations in plasma ultrafiltrate (PUF) and in urine were studied by chromatography coupled to inductively coupled plasma mass spectrometry or to electrospray ionization mass spectrometry. In plasma, four platinum (Pt) compounds were found. The peaks at 200 and 160 kDa corresponding to gamma -globulins contained 40% of the Pt bound; the peak at 60 kDa corresponding to albumin contained 40% of the Pt found. The peak <2 kDa could correspond to oxaliplatin, to its degradation products, or to adducts between Pt compounds and low-molecular-weight species such as glutathione, L-methionine, and L-cysteine. In PUF and urine, oxaliplatin itself, its degradation products, Pt(dach)Cl2, [Pt(dach)(OH2)Cl]+, and species that have the same retention times as Pt(dach)(methionine) and [Pt(dach)]2(glutathione) were found. One hour after infusion, oxaliplatin in PUF and urine represented 12 and 50% of the total Pt, respectively. Three hours after infusion, oxaliplatin, undetectable in PUF, represented 10% of total Pt in urine. Inside red blood cells, two Pt compounds were found. The Pt peak at 60 kDa corresponding to hemoglobin and the peak <2 kDa corresponding to low-molecular species contained, respectively, 60% and 40% of Pt found. This study demonstrates that in the first hours after its infusion, oxaliplatin, in addition to other Pt compounds, is present in plasma and urine and that Pt is bound to albumin, gamma -globulins, and hemoglobin.

Copyright © 2000 by The American Society for Pharmacology and Experimental Therapeutics


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