title: Modeling of pharmaceuticals mixtures toxicity with deviation ratio and best-fit functions models.
abstract: The present study deals with assessment of ecotoxicological parameters of 9 drugs (diclofenac (sodium salt), oxytetracycline hydrochloride, fluoxetine hydrochloride, chloramphenicol, ketoprofen, progesterone, estrone, androstenedione and gemfibrozil), present in the environmental compartments at specific concentration levels, and their mutual combinations by couples against Microtox® and XenoScreen YES/YAS® bioassays. As the quantitative assessment of ecotoxicity of drug mixtures is an complex and sophisticated topic in the present study we have used two major approaches to gain specific information on the mutual impact of two separate drugs present in a mixture. The first approach is well documented in many toxicological studies and follows the procedure for assessing three types of models, namely concentration addition (CA), independent action (IA) and simple interaction (SI) by calculation of a model deviation ratio (MDR) for each one of the experiments carried out. The second approach used was based on the assumption that the mutual impact in each mixture of two drugs could be described by a best-fit model function with calculation of weight (regression coefficient or other model parameter) for each of the participants in the mixture or by correlation analysis. It was shown that the sign and the absolute value of the weight or the correlation coefficient could be a reliable measure for the impact of either drug A on drug B or, vice versa, of B on A. Results of studies justify the statement, that both of the approaches show similar assessment of the mode of mutual interaction of the drugs studied. It was found that most of the drug mixtures exhibit independent action and quite few of the mixtures show synergic or dependent action.
authors.affiliation: Department of Analytical Chemistry, Faculty of Chemistry, Gdańsk University of Technology, 11/12 Narutowicza, 80-233 Gdańsk, Poland.
authors.forename: Monika
authors.initials: M
authors.lastname: Wieczerzak
authors.affiliation: Department of Analytical Chemistry, Faculty of Chemistry, Gdańsk University of Technology, 11/12 Narutowicza, 80-233 Gdańsk, Poland. Electronic address: monwiecz@student.pg.gda.pl.
authors.forename: Błażej
authors.initials: B
authors.lastname: Kudłak
authors.affiliation: Chair of Analytical Chemistry, Faculty of Chemistry and Pharmacy, University of Sofia "St. Kl. Okhridski", 1, J. Bourchier Blvd., 1164 Sofia, Bulgaria.
authors.forename: Galina
authors.initials: G
authors.lastname: Yotova
authors.affiliation: Chair of General and Inorganic Chemistry, Faculty of Chemistry and Pharmacy, University of Sofia "St. Kl. Okhridski", 1, J. Bourchier Blvd., 1164 Sofia, Bulgaria.
authors.forename: Miroslava
authors.initials: M
authors.lastname: Nedyalkova
authors.affiliation: Chair of Analytical Chemistry, Faculty of Chemistry and Pharmacy, University of Sofia "St. Kl. Okhridski", 1, J. Bourchier Blvd., 1164 Sofia, Bulgaria.
authors.forename: Stefan
authors.initials: S
authors.lastname: Tsakovski
authors.affiliation: Chair of Analytical Chemistry, Faculty of Chemistry and Pharmacy, University of Sofia "St. Kl. Okhridski", 1, J. Bourchier Blvd., 1164 Sofia, Bulgaria.
authors.forename: Vasil
authors.initials: V
authors.lastname: Simeonov
authors.affiliation: Department of Analytical Chemistry, Faculty of Chemistry, Gdańsk University of Technology, 11/12 Narutowicza, 80-233 Gdańsk, Poland.
authors.forename: Jacek
authors.initials: J
authors.lastname: Namieśnik
mesh_terms: D048908:Aliivibrio fischeri / Q000187:drug effects*; D004785:Environmental Pollutants / Q000633:toxicity*; D008954:Models, Biological; D004364:Pharmaceutical Preparations / Q000032:analysis*; D018570:Risk Assessment / Q000379:methods; D012441:Saccharomyces cerevisiae / Q000187:drug effects*; D018675:Toxicity Tests
chemical_list: D004785:Environmental Pollutants; D004364:Pharmaceutical Preparations
keywords: Hormones; Interactions modeling; Microtox®; Pharmaceuticals; XenoScreen YES/YAS®