NDLI: Comparative hydrolysis and plasma protein binding of cis-platin and carboplatin in human plasma in vitro.

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Comparative hydrolysis and plasma protein binding of cis-platin and carboplatin in human plasma in vitro.

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Comparative hydrolysis and plasma protein binding of cis-platin and carboplatin in human plasma in vitro.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Sooriyaarachchi, Melani Narendran, Aru Gailer, Jürgen
Description	Country affiliation: Canada Author Affiliation: Sooriyaarachchi M ( Department of Chemistry, University of Calgary, 2500 University Drive NW, Calgary, AB, T2N 1N4, Canada. jgailer@ucalgary.ca.)
Abstract	Platinum-based anti-cancer drugs are widely used to treat cancer in patients, but they also exhibit severe toxic side-effects. Considering that cis-platin and carboplatin are intravenously administered, their biotransformations in the bloodstream are likely to be directly involved in determining their toxic side-effects, but they are poorly understood. We added pharmacologically relevant doses of cis-platin or carboplatin to human plasma from healthy male or female volunteers in vitro at 37 °C and determined the platinum-distribution in plasma after 5 min, 3 h and 24 h using size exclusion chromatography-inductively coupled plasma atomic emission spectrometry (SEC-ICP-AES). The results revealed a negligible inter-individual variation of the platinum-distribution between males and females and faster hydrolysis of cis-platin than carboplatin. Related to this, 95% of platinum was protein-bound 24 h after the addition of cis-platin to plasma, whereas 40% of platinum was protein-bound in the case of carboplatin. Interestingly, cis-platin and carboplatin-derived platinum species appeared to bind to the same 3 plasma proteins at the 3 h time point and thereafter. The analysis of cis-platin and carboplatin-spiked phosphate buffered saline (PBS) revealed a common platinum-containing hydrolysis product that was also detected in plasma. Since cis-platin is associated with more toxic side-effects in patients than carboplatin (even though it is administered at lower doses), our in vitro data suggest that the toxic side-effects of the investigated platinum-drugs may be predominantly determined by the indiscriminate translocation of the parent drugs to malignant and healthy cells. This information may help to mitigate the toxic side-effects of platinum-containing drugs by devising strategies to delay the influx of the parent drugs into non-target tissues.
File Format	HTM / HTML
ISSN	17565901
Issue Number	1
Volume Number	3
e-ISSN	1756591X
Journal	Metallomics
Language	English
Publisher	Royal Society of Chemistry
Publisher Date	2011-01-01
Publisher Place	Great Britain (UK)
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Discipline Biochemistry Antineoplastic Agents Blood Carboplatin Cisplatin Serum Albumin Metabolism Transferrin Chemistry Biotransformation Chromatography, Gel Female Humans Hydrolysis Male Spectrophotometry, Atomic Journal Article Research Support, Non-u.s. Gov't
Content Type	Text
Resource Type	Article
Subject	Chemistry Medicine Metals and Alloys Biochemistry Biomaterials Biophysics

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