RT Journal Article
SR Electronic
T1 Early Biotransformations of Oxaliplatin after Its Intravenous Administration to Cancer Patients
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 1379
OP 1384
VO 28
IS 11
A1 Allain, Pierre
A1 Heudi, Oliver
A1 Cailleux, Annie
A1 Le Bouil, Anne
A1 Larra, Francis
A1 Boisdron-Celle, Michele
A1 Gamelin, Erik
YR 2000
UL http://dmd.aspetjournals.org/content/28/11/1379.abstract
AB 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 γ-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, andl-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, γ-globulins, and hemoglobin. The American Society for Pharmacology and Experimental Therapeutics