title: Early biotransformations of oxaliplatin after its intravenous administration to cancer patients.
abstract: This article deals with the fate of oxaliplatin 1 and 3 h after its i.v. administration (130 mg/m(2)) 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)Cl(2), [Pt(dach)(OH(2))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.
authors.affiliation: Laboratoire de Pharmacologie et Toxicologie, Centre Hospitalier Universitaire, Angers, France. PharmacoToxico@chu-angers.fr
authors.forename: P
authors.initials: P
authors.lastname: Allain
authors.forename: O
authors.initials: O
authors.lastname: Heudi
authors.forename: A
authors.initials: A
authors.lastname: Cailleux
authors.forename: A
authors.initials: A
authors.lastname: Le Bouil
authors.forename: F
authors.initials: F
authors.lastname: Larra
authors.forename: M
authors.initials: M
authors.lastname: Boisdron-Celle
authors.forename: E
authors.initials: E
authors.lastname: Gamelin
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001711:Biotransformation; D001798:Blood Proteins / Q000378:metabolism; D002853:Chromatography, Liquid; D006801:Humans; D007262:Infusions, Intravenous; D013058:Mass Spectrometry; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000077150:Oxaliplatin
chemical_list: D000970:Antineoplastic Agents; D001798:Blood Proteins; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin