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ABSTRACT: The cytotoxic drug, cisplatin (cis-PtCl(2)(NH(3))(2)), has been added to cultures of the marine macroalga, Ulva lactuca, under various experimental conditions. Both accumulation and internalisation over a 48 h period was greater when cisplatin was added to coastal sea water (salinity = 33) from a distilled water solution than when added to either sea water or estuarine water (salinity = 16.5) from a saline solution. This effect is attributed to the greater abundance of the more reactive monoaqua complex (cis-PtCl(OH(2))(NH(3))(2)(+)) in the distilled water solution and kinetic constraints on its conversion back to cis-PtCl(2)(NH(3))(2) in sea water. Despite its mode of action at the cellular level, cisplatin added up to concentrations of 150 nM did not incur a measurable reduction in the efficiency of photochemical energy conversion under any of experimental conditions tested.
Environmental pollution (Barking, Essex: 1987) 09/2011; 159(12):3504-8. · 3.43 Impact Factor
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ABSTRACT: The adsorption of the cytostatic anticancer drug, cisplatin (cis-PtCl(2)(NH(3))(2)), has been studied after its addition to suspensions of estuarine sediment in river water and seawater. After a 16 h reaction period, adsorption was significantly greater in river water (sediment-water distribution coefficient, K(D), of 400 mL g(-1)) than that in seawater (K(D) approximately 150 mL g(-1)) because of the ready aquation of cisplatin to the more reactive monoaquacisplatin (cis-PtCl(OH(2))(NH(3))(2)(+)) at low chloride ion concentrations. Adsorption in river water was enhanced (K(D) approximately 2000 mL g(-1)) by a 24 h period of preincubation in the aqueous phase in which aquation proceeded further. The effects of pH on adsorption were relatively small, presumably because protonation-deprotonation of the particle surface was accompanied by near-equivalent shifts in the charge of hydrolysis products of aquated cisplatin. Kinetic experiments revealed a period of slow protracted uptake (up to about 60 h), followed by gradual desorption in both river water and seawater. Results were interpreted in terms of the formation of monoaquacisplatin, its adsorption to the particle surface, and the subsequent desorption of undefined, unreactive species. Kinetic data were modeled with a sequence of pseudofirst-order reactions and fits were obtained with forward and reverse rate constants for aquation of 1.79 x 10(-5) and 1.84 x 10(-5) s(-1) in river water and 5.50 x 10(-6) and 5.84 x 10(-6) s(-1) in seawater, and adsorption and desorption rate constants of 1.75 x 10(-5) and 0.20 x 10(-5) s(-1) in river water and 0.98 x 10(-5) and 2.8 x 10(-5) s(-1) in seawater. Environmental conditions favoring the retention of cisplatin and its degradation products are low chloride ion concentrations, high turbidities, and long residence or transit times; dispersion of the drug is favored in saline, coastal waters.
Environmental Science and Technology 03/2010; 44(9):3345-50. · 5.23 Impact Factor
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ABSTRACT: In dose-banding (DB) prescribed doses of cancer chemotherapy are fitted to doseranges or 'bands' and standard doses for each band are provided using a selection of pre-filled infusions or syringes, either singly or in combination. DB is used for several drugs where dose is based on body surface area. No DB-scheme has been reported for carboplatin, which, in clinical practice, is routinely dosed according to renal function.
To assess the rationale for DB of carboplatin with regards to factors that influence dosing accuracy, develop a DB scheme, and discuss its potential use and limitations.
Prospective evaluations of carboplatin area under the plasma concentration -- time curve (AUC) following application of the Calvert-formula were identified by a literature search. A relevant carboplatin dose range for construction of a DB-scheme with Calvert-formula based doses was obtained from published glomerular filtration rate distributions for patients receiving carboplatin.
A DB-scheme was developed for individually calculated carboplatin doses of 358-1232 mg, with 35 mg increments between each standard dose and a maximum deviation of 4.7% from prescribed dose. The proposed DB-scheme covers the GFR-ranges 47-221 mL/min and 26-151 mL/min for patients receiving doses based on the target AUCs of 5 and 7 mg/mL/min, respectively.
There is a strong scientific rationale to support DB of carboplatin. The proposed banding scheme could introduce benefits to patients and healthcare staff but, as with other DB schemes, should be validated with prospective clinical and pharmacokinetic studies to confirm safety and efficacy.
Journal of Oncology Pharmacy Practice 07/2007; 13(2):109-17.
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ABSTRACT: To determine the physical and chemical stability of carboplatin infusion for dosebanding, with cycling between refrigerated storage and room temperature in-use conditions.
A sequential study design was selected to closely simulate the temperatures and conditions experienced by drug infusions in pharmaceutical storage and in clinical use. Carboplatin infusions, 0.70 and 2.15 mg/mL, were stored refrigerated for up to 84 days, followed by incubation at 25degreesC for 24 h. The infusions were also returned to refrigerated storage for 3 and 7 days, to replicate a situation in which returned, unused infusions are kept for re-issuing. On pre-determined time-points, infusion chemical and physical stability were determined by HLPC, sub-visual particulate counts, pH-measurement, and weighing of infusions.
Light protected carboplatin infusions at both study concentrations were chemically and physically stable following refrigerated storage for 84 days, followed by a further 24 h under 'in-use' conditions at 25degreesC. Additionally, the infusions were stable following return to refrigerated storage again for at least 7 days.
This study has demonstrated extended stability of carboplatin infusions which enables batch-scale preparation of standard infusions for dose-banding schemes.
Journal of Oncology Pharmacy Practice 07/2007; 13(2):119-26.
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ABSTRACT: This article examines the national systems of technological development in South Korea and Taiwan with particular reference to their semiconductor industries. The article looks at the experiences of South Korea and Taiwan in turn, showing how each of their national approaches to technological development has shaped their indigenous semiconductor industries, leading to the emergence of unique characteristics in both countries. From this discussion, a number of similarities and contrasts are identified between the South Korean and Taiwanese semiconductor industries and the potential for the vigorous and continued development of this important sector in each country is assessed on the basis of their current technological capabilities.
Research Policy. 02/1996;
