DMD Large equally mixed donor pool

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Allain, P.
Right arrow Articles by Gamelin, E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Allain, P.
Right arrow Articles by Gamelin, E.

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


This article has been cited by other articles:


Home page
 NEJMHome page
P. R. Pohlmann, R. L. Mernaugh, L. W. Goff, L. Frati, G. Codacci-Pisanelli, M. S. Copur, M. Norvell, A. Obermiller, F. Loupakis, M. Di Maio, et al.
Chemotherapy and immunotherapy in metastatic colorectal cancer.
N. Engl. J. Med., May 14, 2009; 360(20): 2134 - 2135.
[Full Text] [PDF]

Home page
 Am J Health Syst PharmHome page
P. Andre, S. Cisternino, A.-L. Roy, F. Chiadmi, J. Schlatter, P. Agranat, O. Fain, and J.-E. Fontan
Stability of oxaliplatin in infusion bags containing 5% dextrose injection
Am. J. Health Syst. Pharm., September 15, 2007; 64(18): 1950 - 1954.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
C. H. Takimoto, M. A. Graham, G. Lockwood, C. M. Ng, A. Goetz, D. Greenslade, S. C. Remick, S. Sharma, S. Mani, R. K. Ramanathan, et al.
Oxaliplatin Pharmacokinetics and Pharmacodynamics in Adult Cancer Patients with Impaired Renal Function
Clin. Cancer Res., August 15, 2007; 13(16): 4832 - 4839.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
T. W. Synold, C. H. Takimoto, J. H. Doroshow, D. Gandara, S. Mani, S. C. Remick, D. L. Mulkerin, A. Hamilton, S. Sharma, R. K. Ramanathan, et al.
Dose-Escalating and Pharmacologic Study of Oxaliplatin in Adult Cancer Patients with Impaired Hepatic Function: A National Cancer Institute Organ Dysfunction Working Group Study
Clin. Cancer Res., June 15, 2007; 13(12): 3660 - 3666.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Chem.Home page
J. Peng, R. Mandal, M. Sawyer, and X.-F. Li
Characterization of Intact Hemoglobin and Oxaliplatin Interaction by Nanoelectrospray Ionization Tandem Mass Spectrometry
Clin. Chem., December 1, 2005; 51(12): 2274 - 2281.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
J. Turkson, S. Zhang, L. B. Mora, A. Burns, S. Sebti, and R. Jove
A Novel Platinum Compound Inhibits Constitutive Stat3 Signaling and Induces Cell Cycle Arrest and Apoptosis of Malignant Cells
J. Biol. Chem., September 23, 2005; 280(38): 32979 - 32988.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
C. H. Takimoto, S. C. Remick, S. Sharma, S. Mani, R. K. Ramanathan, J. Doroshow, A. Hamilton, D. Mulkerin, M. Graham, G. F. Lockwood, et al.
Dose-Escalating and Pharmacological Study of Oxaliplatin in Adult Cancer Patients With Impaired Renal Function: A National Cancer Institute Organ Dysfunction Working Group Study
J. Clin. Oncol., July 15, 2003; 21(14): 2664 - 2672.
[Abstract] [Full Text] [PDF]


Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

Copyright © 2000 by the American Society for Pharmacology and Experimental Therapeutics.