European Journal of Clinical Pharmacology

, Volume 75, Issue 10, pp 1355–1360 | Cite as

Pharmacokinetic study of imrecoxib in patients with renal insufficiency

  • Qi Pei
  • Jin-lian Xie
  • Jie Huang
  • Wen-yu Liu
  • Xiao-yan Yang
  • Yan Wang
  • Wei Li
  • Hong-yi Tan
  • Hao ZhangEmail author
  • Guo-Ping YangEmail author
Clinical Trial



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.


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.


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).


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.


Imrecoxib Renal insufficiency Pharmacokinetics Cyclooxygenase 2 inhibitors 



This study was supported by International Science & Technology Cooperation Program of China (No.2014DFA30900) and Scientific Foundation of Hunan Province (No.2015TP2005).

Authorship contributions

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.

Compliance with ethical standards

Conflict of interests

There are no competing interests to declare.

Ethical approval

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 [] number ChiCTR-RPC-17013177) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Supplementary material

228_2019_2698_MOESM1_ESM.docx (18 kb)
ESM 1 (DOCX 17 kb)
228_2019_2698_MOESM2_ESM.doc (140 kb)
ESM 2 (DOC 140 kb)


  1. 1.
    Pereira D, Peleteiro B, Araujo J et al (2011) The effect of osteoarthritis definition on prevalence and incidence estimates: a systematic review. Osteoarthr Cartil 19(11):1270–1285CrossRefGoogle Scholar
  2. 2.
    Felson DT, Lawrence RC, Dieppe PA et al (2000) Osteoarthritis: new insights. Part 1: the disease and its risk factors. Ann Intern Med 133(8):635–646CrossRefGoogle Scholar
  3. 3.
    Lawrence RC, Felson DT, Helmick CG et al (2008) Estimates of the prevalence of arthritis and other rheumatic conditions in the United States: part II. Arthrit Rheumat 58(1):26–35CrossRefGoogle Scholar
  4. 4.
    Oliveria SA, Felson DT, Reed JI et al (1995) Incidence of symptomatic hand, hip, and knee osteoarthritis among patients in a health maintenance organization. Arthrit Rheumat 38(8):1134–1141CrossRefGoogle Scholar
  5. 5.
    Lanas A (2010) A review of the gastrointestinal safety data-a gastroenterologist’s perspective. Rheumatology 49[Suppl 2]:ii3–ii10Google Scholar
  6. 6.
    Silverstein FE, Faich G, Goldstein JL et al (2000) Gastrointestinal toxicity with celecoxib vs nonsteroidal anti-inflammatory drugs for osteoarthritis and rheumatoid arthritis: the CLASS study: a randomized controlled trial. J Am Med Assoc 284(10):1247–1255CrossRefGoogle Scholar
  7. 7.
    Huang J, Gu J, Pan Y et al (2011) A multicenter, double-blind and randomized controlled PhaseIItrial of Imrecoxib in treatment of knee osteoarthritis. Chin Pharmaceut J 46(22):1740–1745 (in Chinese)Google Scholar
  8. 8.
    Hou X, Zhou J, Yu S et al (2018) Differences in the in vivo and in vitro metabolism of imrecoxib in humans: formation of the rate-limiting aldehyde intermediate. Drug Metab Dispos 46(9):1320–1328CrossRefGoogle Scholar
  9. 9.
    Feng Z, Chu F, Guo Z et al (2009) Synthesis and anti-inflammatory activity of the major metabolites of imrecoxib. Bioorg Med Chem Lett 19(8):2270–2272CrossRefGoogle Scholar
  10. 10.
    Guo ZR (2012) Discovery of imrecoxib. Chin J New Drugs 21(3):223–230 (in Chinese)Google Scholar
  11. 11.
    Singh G, Miller JD, Lee FH et al (2002) Prevalence of cardiovascular disease risk factors among US adults with self-reported osteoarthritis: data from the third National Health and Nutrition Examination Survey. Am J Manag Care 8S(15):S383–S391Google Scholar
  12. 12.
    Leblond FA, Giroux L, Villeneuve JP et al (2000) Decreased in vivo metabolism of drugs in chronic renal failure. Drug Metab Dispos 28(11):1317–1320Google Scholar
  13. 13.
    De Martin S, Orlando R, Bertoli M et al (2006) Differential effect of chronic renal failure on the pharmacokinetics of lidocaine in patients receiving and not receiving hemodialysis. Clin Pharmacol Ther 80(6):597–606CrossRefGoogle Scholar
  14. 14.
    Rios A, Vargas-Robles H, Maria Gamez-Mendez A et al (2012) Cyclooxygenase-2 and kidney failure. Prostaglandins Other Lipid Mediat 98(3-4SI):86–90CrossRefGoogle Scholar
  15. 15.
    Michels WM, Grootendorst DC, Verduijn M et al (2010) Performance of the Cockcroft-gault, MDRD, and new CKD-EPI formulas in relation to GFR, age, and body size. Clin J Am Soc Nephrol 5(6):1003–1009CrossRefGoogle Scholar
  16. 16.
    Nolin TD, Frye RF, Le P et al (2009) ESRD impairs nonrenal clearance of fexofenadine but not midazolam. J Am Soc Nephrol 20(10):2269–2276CrossRefGoogle Scholar
  17. 17.
    Smith WB, Mannaert E, Verhaeghe T et al (2012) Effect of renal impairment on the pharmacokinetics of prucalopride: a single-dose open-label phase I study. Drug Design Dev Ther 6:407Google Scholar
  18. 18.
    Murphy EJ (2005) Acute pain management pharmacology for the patient with concurrent renal or hepatic disease. Anaesth Intensive Care 33(3):311CrossRefGoogle Scholar
  19. 19.
    Cawello W, Fuhr U, Hering U et al (2013) Impact of impaired renal function on the pharmacokinetics of the antiepileptic drug lacosamide. Clin Pharmacokinet 52(10):897–906CrossRefGoogle Scholar
  20. 20.
    Phelan M, Anzures-Cabrera J, Carlile DJ et al (2013) Effect of hepatic and renal impairment on the pharmacokinetics of Dalcetrapib. Clin Pharmacokinet 52(4):255–265CrossRefGoogle Scholar
  21. 21.
    Katz JA (2013) COX-2 inhibition: what we learned-a controversial update on safety data. Pain Med 14[Suppl 1]:S29–S34CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Center for Clinical Pharmacology, The Third Xiangya HospitalCentral South UniversityChangshaChina
  2. 2.School of Pharmaceutical ScienceCentral South UniversityChangshaChina
  3. 3.Department of Nephrology, The Third Xiangya HospitalCentral South UniversityChangshaChina

Personalised recommendations