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In Vitro Assessment of the Formation of Ceftriaxone-Calcium Precipitates in Human Plasma

Schmutz, Hans-Rudolf and Detampel, Pascal and Bühler, Theo and Büttler, André and Gygax, Benjamin and Huwyler, Jörg. (2011) In Vitro Assessment of the Formation of Ceftriaxone-Calcium Precipitates in Human Plasma. Journal of pharmaceutical sciences, Vol. 100, H. 6. pp. 2300-2310.

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Official URL: http://edoc.unibas.ch/dok/A5841178

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Abstract

Ceftriaxone is a third-generation cephalosporin antibiotic, which has a broad spectrum of bactericidal activity. Ceftriaxone is highly soluble as a sodium salt, but far less soluble as a calcium salt. Incompatibility of ceftriaxone with calcium and the possible formation of precipitates have been stated in the product label from early on. It was the objective of the present in vitro study to further assess the risk of precipitation of calcium-ceftriaxone in human plasma. Analytical methods were developed (high-performance liquid chromatography and flame atomic absorption spectroscopy) to quantitate calcium and ceftriaxone in human plasma supernatants and human plasma precipitates. Using high concentrations of ceftriaxone (10 mmol/l) and calcium (4.2 mmol/l) did not result in any precipitation after a 2-h incubation in human plasma at 37°C. Under conditions of forced precipitations only formation of precipitation was observed. The identity of the precipitated material was confirmed by Energy Dispersive X-Ray Analysis and Fourier Transform Infrared Spectroscopy. We conclude that calcium-ceftriaxone in human plasma has an apparent kinetic solubility product constant of greater than 0.42 x 10-4 (mol/l)2, which exceeds the normal thermodynamic solubility product in water by a factor of 26. Under these conditions, formation of plasma precipitates is unlikely.
Faculties and Departments:05 Faculty of Science > Departement Pharmazeutische Wissenschaften > Pharmazie > Pharmazeutische Technologie (Huwyler)
UniBasel Contributors:Detampel, Pascal and Huwyler, Jörg
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:American Pharmaceutical Association
ISSN:0022-3549
Note:Publication type according to Uni Basel Research Database: Journal article
Last Modified:14 Sep 2012 07:17
Deposited On:14 Sep 2012 06:40

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