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Transformation of bisphosphonates into insoluble material in human blood in vitro
1998 (English)In: Methods and Findings in Experimental and Clinical Pharmacology, ISSN 0379-0355, E-ISSN 2013-0155, Vol. 20, no 4, p. 289-295Article in journal (Refereed) Published
Abstract [en]

The aim of the study was to find out whether bisphosphonates transform into insoluble material in human blood and serum in vitro. Samples of fresh blood and serum were incubated with various concentrations of 14C-labelled clodronate, etidronate, pamidronate and tiludronate for 2 h and 8 h at 37 °C. The presence of unfiltrable material in the plasma separated from the blood, and in the serum were studied with 1) 100, 300 and 1,000 kd (kilo Daltons) filter tubes centrifuged at 3,000 g for 60 min, and 2) high-speed centrifugation at 13,000 g for 30 min. The radioactivities in the ultrafiltrates and supernatants were compared to those in the native plasma or serum. All bisphosphonates transformed into unfiltrable material, which was separated from the samples with the 100 and 300 kd filters but not with the 1,000 kd filter. The material was not sedimented with the high-speed centrifugation. The lengthening of the incubation time from 2 h to 8 h increased the unfiltrable fraction, which generally was dependent on the drug concentration in the blood, too. However, the fraction of the unfiltrable material did not seem to increase with time when the drug was incubated with serum instead of blood. Since drug binding to plasma proteins is generally a very rapid process, some factors other than proteins only, e.g. cations or cation residues, present in the blood but not in the serum, should be involved in transforming of bisphosphonates into insoluble material in the blood.

Place, publisher, year, edition, pages
1998. Vol. 20, no 4, p. 289-295
Keywords [en]
Bisphosphonates, Drug transformation, Protein binding, bisphosphonic acid derivative, clodronic acid, etidronic acid, pamidronic acid, plasma protein, tiludronic acid, article, blood, blood sampling, drug binding, drug blood level, female, human, male, normal human, radioactivity, serum, Analgesics, Non-Narcotic, Antineoplastic Agents, Biotransformation, Carbon Radioisotopes, Diphosphonates, Humans
National Category
Public Health, Global Health, Social Medicine and Epidemiology
Identifiers
URN: urn:nbn:se:mdh:diva-55607DOI: 10.1358/mf.1998.20.4.485682ISI: 000074262700002Scopus ID: 2-s2.0-0031812734OAI: oai:DiVA.org:mdh-55607DiVA, id: diva2:1585373
Available from: 2021-08-17 Created: 2021-08-17 Last updated: 2022-03-18Bibliographically approved

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Kautiainen, Susanna

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