Skip to main content

Advertisement

SpringerLink
Log in

Optimizing the dose of mycophenolate mofetil for the maintenance treatment of lupus nephritis by therapeutic drug monitoring

  • Brief Report
  • Published:
Clinical Rheumatology Aims and scope Submit manuscript

Abstract

To evaluate the usefulness of monitoring the pharmacokinetic of mycophenolic acid (MPA) in lupus nephritis (LN), in order to optimize the mycophenolate mofetil (MMF) dose in the single patient. Five consecutive patients with active LN were studied. After standard induction therapy with MMF, MMF was titrated to achieve a stable target of MPA-AUC0-12h of 45–60 mg.h/l during the maintenance treatment. For MPA assays, blood samples were collected at 0, ½, 1 ¼, 2, 4, 6, 8 and 12 h after the morning dose. Plasma MPA concentration was measured using a validated high-performance liquid chromatography. Treatment response was evaluated at baseline, i.e. at the end of the induction therapy and during maintenance therapy with MMF. The average whole follow-up was 21.4 months. At the last visit, a complete renal response was registered in all the five patients. No renal flares were observed. Glucocorticoids were suspended in all. The mean MPA-AUC0-12h of MMF at the last visit [56.74 (±2.9) mg.h/l] was significantly lower than MPA-AUC0-12h at baseline [98.7 (±24.6) mg.h/l] (p = 0.009), since the dose of MMF was significantly reduced in all the patients [from 2.8 g/day (±0.4) to 1.9 g/day (±0.4) (p = 0.018)] based on the target MPA-AUC. No severe adverse events were observed. Assessment of MPA pharmacokinetics may be useful to optimize the maintenance therapy of lupus nephritis with MMF, possibly improving the efficacy and minimizing the side effects.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Appel GB, Contreras G, Dooley MA et al (2009) Mycophenolate mofetil or intravenous cyclophosphamide for induction treatment of lupus nephritis. J Am Soc Nephrol 20:1103–1112

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  2. Dooley MA, Jayne D, Ginzler EM et al (2011) Mycophenolate versus azathioprine as maintenance therapy for lupus nephritis. N Engl J Med 365(20):1886–189

    Article  CAS  PubMed  Google Scholar 

  3. Houssiau FA, D’Cruz D, Sangles S et al (2010) Azathioprine versus mycophenolate mofetil for long-term immunosuppression in lupus nephritis: results from the MAINTAIN Nephritis Trial. Ann Rheum Dis 69(12):2083–2089

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  4. Le Meur Y, Buchler M, Thierry A et al (2007) Individualized mycophenolate mofetil dosing based on drug exposure significantly improves patients outcomes after renal transplantation. Am J Transplant 7:2496–2503

    Article  PubMed  Google Scholar 

  5. Lertdumrongluk P, Somparn P (2010) Pharmacokinetics of mycophenolic acid in severe lupus nephritis. Kidney Int 78:389–395

    Article  CAS  PubMed  Google Scholar 

  6. Kittanamongkolchai W, Rukrung C (2013) Therapeutic drug monitoring of mycophenolate mofetil for the treatment of severely active lupus nephritis. Lupus 7:727–732

    Article  Google Scholar 

  7. Zahr N, Arnaud L, Marquet P et al (2010) Mycophenolic acid area under the curve correlates with disease activity in lupus patients treated with mycophenolate mofetil. Arthritis Rheum 62:2047–2054

    CAS  PubMed  Google Scholar 

  8. Daleboudt GM, Reinders ME, den Hartigh J et al (2013) Concentration-controlled treatment of lupus nephritis with mycophenolate mofetil. Lupus 22:171–179

    Article  CAS  PubMed  Google Scholar 

  9. Tan EM, Cohen AS, Fries JF et al (1982) The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 25:1271–1277

    Article  CAS  PubMed  Google Scholar 

  10. Weening JJ, D’agati VD, Schwartz MM et al (2004) The classification of glomerulonephritis in systemic lupus erytematosus. J Am Soc Nephrol 15:241–250

    Article  PubMed  Google Scholar 

  11. Shaw LM, Korecka M, Van Breeman R (1998) Analysis, pharmacokinetics and therapeutic drug monitoring of mycophenolic acid. Clin Biochem 31:323–328

    Article  CAS  PubMed  Google Scholar 

  12. Baraldo M, Isola M, Feruglio MT et al (2005) Therapeutic mycophenolic acid monitoring by means of limited sampling strategy in orthotopic heart transplantation patients. Transplant Proc 37:2240–2243

    Article  CAS  PubMed  Google Scholar 

  13. Bertsias GK, Tektonidou M, Amoura Z et al (2012) Joint European League Against Rheumatism and European Renal Association-European Dialysis and Transplant Association (EULAR/ERA-EDTA) recomendations for the management of adult and pediatric lupus nephritis. Ann Rheum Dis 71:1771–1782

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  14. Van Gelder T, Le Meur Y, Shaw LM (2006) Therapeutic drug monitoring of mycophenolate mofetil in transplantation. Ther Drug Monit 28:145–154

    Article  PubMed  Google Scholar 

  15. Laskari K, Mavragani CP, Tzioufas AG, Moutsopoulos HM (2010) Mycophenolate mofetil as maintenance therapy for proliferative lupus nephritis: a long-term observational prospective study. Arthritis Res Ther 12:R208

    Article  PubMed Central  PubMed  Google Scholar 

Download references

Conflict of interest

None.

Author information

Authors and Affiliations

  1. Rheumatology Clinic, DSMB, University of Udine, AOU “Santa Maria della Misericordia”, Udine, Italy

    A. Zabotti, L. Quartuccio, S. Sacco, G. De Marchi & S. De Vita

  2. Institute of Clinical Pharmacology and Toxicology, University of Udine, AOU “Santa Maria della Misericordia”, Udine, Italy

    M. Baraldo

Authors
  1. A. Zabotti
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M. Baraldo
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. L. Quartuccio
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. S. Sacco
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. G. De Marchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. S. De Vita
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to S. De Vita.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zabotti, A., Baraldo, M., Quartuccio, L. et al. Optimizing the dose of mycophenolate mofetil for the maintenance treatment of lupus nephritis by therapeutic drug monitoring. Clin Rheumatol 34, 171–174 (2015). https://doi.org/10.1007/s10067-014-2786-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10067-014-2786-9

Keywords

Search

Navigation