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概要
Physicochemical Properties of Causative Drugs Associated with Renal Nephrotoxicity
Reiko Yano, Fumiko Ohtsu and Nobuyuki Goto
Background: In this study, we examined the association between drug-induced renal nephrotoxicity and the physiochemical properties of the causative drugs we extracted from CARPIS in order to provide drug information about potential severe risks at the time of and after marketing approval.
Methods: We designated the nephrotoxicity-associated drugs as the case drug group (126 drugs), and all other drugs were set as the control drug group (915 drugs). We compared the physicochemical properties of the group. We performed univariate logistic regression analysis on each investigation item, and then performed multivariate stepwise logistic regression analysis on the items which were p<0.2 using univariate logistic regression analysis.
Results: Model 1, which uses a logP value, showed that the odds ratio of pKa at less than 7 was 2.46, and that at less than 7-8 was 2.01. The odds ratio of logP value at less than 0 was 1.67. MW at less than 300-400 was 0.57. Model 2, which uses a logD value, showed that logD at less than 0 was 2.23. The odds ratio of pKa at less than 7 was 2.34, and at less than 7-8 was 2.04. The odds ratio of MW at less than 300-400 was 0.56.
Conclusion: The results clearly showed the risk of renal problems associated with water-soluble drugs. The information could be useful to consider potential risks of renal problems associated with water-soluble drugs at the time of drug approval and after marketing and to compensate for the lack of information.