Abstract
Objective
Renal insufficiency may influence the pharmacokinetics of drugs. We have investigated the pharmacokinetic parameters of imrecoxib and its two main metabolites in individuals with osteoarthritis (OA) with normal renal function and renal insufficiency, respectively.
Methods
This was a prospective, parallel, open, matched-group study in which 24 subjects were enrolled (renal insufficiency group, n = 12; healthy control group, n = 12). Blood samples of subjects administered 100 mg imrecoxib were collected at different time points and analyzed. Plasma concentrations of imrecoxib and its two metabolites (M1 and M2) were determined by the liquid chromatography-tandem mass spectrometry method, and pharmacokinetic parameters (clearance [CL], apparent volume of distribution [Vd], maximum (or peak) serum concentration [Cmax], amount of time drug is present in serum at Cmax [Tmax], area under the curve [AUC; total drug exposure across time], mean residence time [MRT] and elimination half-life [t1/2]) were calculated.
Results
The demographic characteristics of the two groups were not significantly different, with the exception of renal function. The mean Cmax and AUC0-t (AUC from time 0 to the last measurable concentration) of imrecoxib in the renal insufficiency group were 59 and 70%, respectively, of those of the healthy control volunteers with normal renal function, indicating a significant decline in the former group (P < 0. 05). The mean pharmacokinetic parameters of Ml in the renal insufficiency and healthy control groups did not significantly differ. In contrast, the mean Cmax and AUC0-t of M2 in the renal insufficiency group were 233 and 367%, respectively, of those of the normal renal function group, indicating a significant increase in the former group (P < 0.05). The mean CL/F (clearance/bioavailability) of M2 of the renal insufficiency group was 37% of that of the normal renal function group, indicating a notable reduction in the former group (P < 0.05).
Conclusion
The exposure of imrecoxib in OA patients with renal insufficiency showed a decline compared to that in healthy subjects. However, in patients with renal insufficiency the exposure of M2 was markedly increased and the CL was noticeably reduced. These results indicate that the dosage of imrecoxib should be reduced appropriately in patients with renal insufficiency.
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Acknowledgements
This study was supported by International Science & Technology Cooperation Program of China (No.2014DFA30900) and Scientific Foundation of Hunan Province (No.2015TP2005).
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Qi Pei, responsible for data analysis, article writing; Jin-lian Xie, responsible for article modification and plasma sample analysis;
Jie Huang, responsible for data analysis; Wen-yu Liu, responsible for case collection, data analysis, article writing; Xiao-yan Yang, Yan Wang, Wei Li, responsible for article modification; Hong-yi Tan, responsible for plasma sample analysis;
Hao Zhang, responsible for scheme design, Quality Supervision. Guo-Ping Yang, responsible for scheme design, Quality Supervision.
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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee (Chinese Clinical Trial Registry [http://www.chictr.org.cn] number ChiCTR-RPC-17013177) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
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Pei, Q., Xie, Jl., Huang, J. et al. Pharmacokinetic study of imrecoxib in patients with renal insufficiency. Eur J Clin Pharmacol 75, 1355–1360 (2019). https://doi.org/10.1007/s00228-019-02698-x
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DOI: https://doi.org/10.1007/s00228-019-02698-x