Therapeutic durg monitoring of cyclosporin using area under the curve in nephrotic syndrome

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Published Jun 24, 2019
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Vol. 97 No. 2 (2019): Issue Feb 2019

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Emna Gaies
Mouna Ben Sassi
Rim Charfi
Isssam Salouage
Nadia Jebabli
Hanéne ElJebari
Anis Klouz
Riadh Daghfous
Sameh Trabelsi

Abstract

The use of cyclosporin in nephrotic syndrome can be considered in cortico-resistance or cortico-dependence. Cyclosporin is an immunosuppressant with a narrow therapeutic range and large pharmacokinetics variability justifying its therapeutic drug monitoring (TDM).
The aim of this study was to evaluate the TDM of cyclosporin by the measurement of AUC0-12h in patients with nephrotic syndrome and to study the correlations between the AUC0-12h and the different blood concentrations of cyclosporin.
It is a retrospective study from 2009 to 2016. TDM of cyclosporin was carrying out by ARCHITECT®. Determination of the AUC0-12h was made from three samples taken at T0, T60min and T180min obtained by a model of population pharmacokinetics of cyclosporin.
A total of 20 patients were evaluated (29 abbreviated kinetics). The median AUC0-12h was 4.76 mg*h/L. Considering the target 5 mg*h/L during the first 6 months, 6 AUC0-12h were sub-therapeutic and 5 supra-therapeutic, no AUC0-12h was in the therapeutic range. Considering the 3 mg*h/L as a target during the following months, 13 AUC0-12h among 18 were supra-therapeutic.
A correlation coefficient between the AUC0-12h of cyclosporin and C0 was 0.798. Correlation between AUC0-12h and C2h was 0.909. The median C2h found in our work was 878 ng / mL during the first six months versus 1039 ng / mL in the following months.
Our patients are overexposed to cyclosporin and TDM of this drug by determination of AUC0-12h or by C2h would be more interesting than TDM by C0. TDM allows a better individual dose adjustment to avoid especially toxicity of cyclosporin.

Keywords:

Cyclosporine, nephrotic syndrome, therapeutic monitoring, concentration, area under the curve

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References

  1. Briggs WA, Gao ZH, Xing JJ, Scheel PJ, Gimenez LF, Samaniego MD, et al. Suppression of dialysis patients' lymphocyte IL-2R expression byglucocorticoids and cyclosporine. Cytokine. 1997;9(8):624-8.
  2. Desassis JF, Raats CJ, Bakker MA, van den Born J, Berden JH. Antiproteinuric effect of ciclosporin A in adriamycin nephropathy in rats. Nephron. 1997; 75 (3):336-41.
  3. Gaïes E, Eljebari H, Bacha MM, Woillard JB, Jebabli N, Helal I et al. Cyclosporine (Equoral®) Population Pharmacokinetics and Bayesian Estimation in Tunisian Renal Transplant Recipients. Enliven: Surgery and Transplantation. 2015;1(1):1-7.
  4. Iijima K, Sako M, Oba MS, Ito S, Hataya H, Tanaka R et al. Cyclosporine C2 monitoring for the treatment of frequently relapsing nephrotic syndrome in children: a multicenter randomized phase II trial.Clin J Am Soc Nephrol. 2014;9(2):271-8.
  5. Medeiros M, Perez-Urizar J, Mejía-Gaviria N, Ramirez-López E, Castaneda-Hernández G, Munoz R. Decreased cyclosporine exposure during the remission of nephrotic syndrome. Pediatr Nephrol. 2007;22:84-90.
  6. Meyrier A, Niaudet P. Minimal change and Focal-segmental glomerulosclerosis. In : AM Davidson, JS Cameron, JP Grunfeld, E Ritz, C Van Ypersele, C Ponticelli and C Winearls Eds. Oxford textbook of clinical Nephrology, 3rd edition. Oxford, Oxford University Press. 2005;1:439-469.
  7. Deschênes G, Leclerc A. Épidémiologie du syndrome néphrotique de l'enfant. Archives de Pédiatrie. 2010;17:622-623.
  8. Filler G. How should microemulsified Cyclosporine A (Neoral) therapy in patients with nephrotic syndrome be monitored? Nephrol Dial Transplant. 2005 Jun; 20(6):1032-4.
  9. Naito M, Takei T, Eguchi A, Uchida K, Tsuchiya K, Nitta K. Monitoring of blood cyclosporine concentration in steroid-resistant nephrotic syndrome. Intern Med. 2008; 47(18):1567-72.
  10. Rinaldi S, Sesto A, Barsotti P, Faraggiana T, Sera F, Rizzoni G. Cyclosporine therapy monitored with abbreviated area under curve in nephrotic syndrome. Pediatr Nephrol. 2005;20(1):25-9.
  11. Niaudet P, Reigneau O, Humbert H. A pharmacokinetic study of Neoral in childhood steroid-dependent nephrotic syndrome. Pediatr Nephrol. 2001;16 :154-5.
  12. Saito T, Iwano M, Matsumoto K, Mitarai T, Yokoyama H, Yorioka N et al. Significance of combined cyclosporine−prednisolone therapy and cyclosporine blood concentration monitoring for idiopathic membranous nephropathy with steroid-resistant nephrotic syndrome: a randomized controlled multicenter trial.Clin Exp Nephrol. 2014;18 (5):784-94.