Population pharmacokinetics of ciclosporin in haematopoietic allogeneic stem cell transplantation with emphasis on limited sampling strategy

British Journal of Clinical Pharmacology

Volumn 73, Issue 4, 2012, Pages 553-563

  Wilhelm, Abraham J ^a   de Graaf, Peer ^a   Veldkamp, Agnes I ^a   Janssen, Jeroen J W M ^a   Huijgens, Peter C ^a   Swart, Eleonora L ^a  

^a VU UNIVERSITY MEDICAL CENTER   (Netherlands)

Author keywords

Bayesian; Ciclosporin; Limited sampling strategy; NONMEM; Peripheral blood stem cell transplantation; Population pharmacokinetics

Indexed keywords

ALANINE AMINOTRANSFERASE; ALBUMIN; ASPARTATE AMINOTRANSFERASE; CIPROFLOXACIN; COTRIMOXAZOLE; CREATININE; CYCLOPHOSPHAMIDE; CYCLOSPORIN A; FLUCONAZOLE; FLUDARABINE; PHENETICILLIN; VALACICLOVIR;

ACUTE GRANULOCYTIC LEUKEMIA; ADULT; AGED; ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION; ANTIBIOTIC PROPHYLAXIS; AREA UNDER THE CURVE; ARTICLE; BAYES THEOREM; BLOOD SAMPLING; BODY WEIGHT; BOOTSTRAPPING; CANCER RADIOTHERAPY; CHRONIC LYMPHOBLASTIC LEUKEMIA; CLINICAL ARTICLE; COMPARTMENT MODEL; CREATININE BLOOD LEVEL; DRUG ABSORPTION; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG DISTRIBUTION; FEMALE; FLUORESCENCE POLARIZATION IMMUNOASSAY; GRAFT VERSUS HOST REACTION; HEMATOCRIT; HEMATOLOGIC MALIGNANCY; HUMAN; KIDNEY FUNCTION; LIVER FUNCTION; MALE; MULTIMODALITY CANCER THERAPY; MYELOABLATIVE CONDITIONING; NONHODGKIN LYMPHOMA; PHARMACOEPIDEMIOLOGY; PRIORITY JOURNAL; RADIATION DOSE; WHOLE BODY RADIATION;

ADOLESCENT; ADULT; AGED; AREA UNDER CURVE; BAYES THEOREM; BIOLOGICAL AVAILABILITY; CYCLOSPORINE; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG MONITORING; FEMALE; GRAFT VS HOST DISEASE; HEMATOPOIETIC STEM CELL TRANSPLANTATION; HUMANS; IMMUNOSUPPRESSIVE AGENTS; MALE; MIDDLE AGED; MODELS, BIOLOGICAL; PROSPECTIVE STUDIES; SAMPLING STUDIES; TRANSPLANTATION, HOMOLOGOUS; YOUNG ADULT;

EID: 84858246928     PISSN: 03065251     EISSN: 13652125     Source Type: Journal    
DOI: 10.1111/j.1365-2125.2011.04116.x     Document Type: Article

References (59)

1. Kersey JH. The role of allogeneic-cell transplantation in leukemia. N Engl J Med 2010; 363: 2158-9.
2. Oshima K, Hanada R, Kobayashi R, Kato K, Nagatoshi Y, Tabuchi K, Kato S. Hematopoietic stem cell transplantation in patients with severe congenital neutropenia: an analysis of 18 Japanese cases. Pediatr Transplant 2010; 14: 657-63.
3. Hogan WJ, Storb R. Use of cyclosporine in hematopoietic cell transplantation. Transplant Proc 2004; 36: S367-S371.
4. Duncan N, Craddock C. Optimizing the use of cyclosporin in allogeneic stem cell transplantation. Bone Marrow Transplant 2006; 38: 169-74.
5. Hermann M, Kase ET, Molden E, Christensen H. Evaluation of microsomal incubation conditions on CYP3A4-mediated metabolism of cyclosporine A by a statistical experimental design. Curr Drug Metab 2006; 7: 265-71.
6. Kelly PA, Wang H, Napoli KL, Kahan BD, Strobel HW. Metabolism of cyclosporine by cytochromes P450 3A9 and 3A4. Eur J Drug Metab Pharmacokinet 1999; 24: 321-8.
7. Funk C. The role of hepatic transporters in drug elimination. Expert Opin Drug Metab Toxicol 2008; 4: 363-79.
8. Belitsky P, Dunn S, Johnston A, Levy G. Impact of absorption profiling on efficacy and safety of cyclosporin therapy in transplant recipients. Clin Pharmacokinet 2000; 39: 117-25.
9. Dotti G, Gaspari F, Caruso R, Perico N, Remuzzi G, Barbui T, Rambaldi A. Pharmacokinetic study of the new cyclosporine-A formulation (Neoral) in adult allogeneic bone marrow transplant recipients. Haematologica 2001; 86: 311-5.
10. Hesselink DA, van Schaik RH, van der Heiden IP, van der Werf M, Gregoor PJ, Lindemans J, Weimar W, van Gelder T. Genetic polymorphisms of the CYP3A4, CYP3A5, and MDR-1 genes and pharmacokinetics of the calcineurin inhibitors cyclosporine and tacrolimus. Clin Pharmacol Ther 2003; 74: 245-54.
11. Schwinghammer TL, Przepiorka D, Venkataramanan R, Wang CP, Burckart GJ, Rosenfeld CS, Shadduck RK. The kinetics of cyclosporine and its metabolites in bone marrow transplant patients. Br J Clin Pharmacol 1991; 32: 323-8.
12. Kahan BD, Keown P, Levy GA, Johnston A. Therapeutic drug monitoring of immunosuppressant drugs in clinical practice. Clin Ther 2002; 24: 330-50.
13. Abendroth D. Experience with therapeutic drug monitoring of cyclosporine. Transplant Proc 2004; 36: 426S-9S.
14. Zielinska T, Zakliczynski M, Szewczyk M, Zielinska-Kukla A, Foremny J, Kalarus Z, Religia Z, Zembala M. Influence of long term cyclosporine therapy on insulin and its precursors secretion in patients after heart transplantation. Ann Transplant 2003; 8: 10-2.
15. Kahan BD. Optimization of cyclosporine therapy. Transplant Proc 1993; 25: 5-9.
16. Lassila M, Santisteban J, Finckenberg P, Salmenpera P, Riutta A, Moilanen E, Virtanen I, Vapaatalo H, Nurminen ML. Vascular changes in cyclosporine A-induced hypertension and nephrotoxicity in spontaneously hypertensive rats on high-sodium diet. J Physiol Pharmacol 2001; 52: 21-38.
17. Elmaagacli AH, Beelen DW, Trenn G, Schmidt O, Nahler M, Schaefer UW. Induction of a graft-versus-leukemia reaction by cyclosporin A withdrawal as immunotherapy for leukemia relapsing after allogeneic bone marrow transplantation. Bone Marrow Transplant 1999; 23: 771-7.
18. Maloney DG. Graft-vs.-lymphoma effect in various histologies of non-Hodgkin's lymphoma. Leuk Lymphoma 2003; 44: (Suppl. 3): S99-105.
19. Corradini P, Tarella C, Olivieri A, Gianni AM, Voena C, Zallio F, Ladetto M, Falda M, Lucesole M, Dodero A, Ciceri F, Benedetti F, Rambaldi A, Sajeva MR, Tresoldi M, Pileri A, Bordignon C, Bregni M. Reduced-intensity conditioning followed by allografting of hematopoietic cells can produce clinical and molecular remissions in patients with poor-risk hematologic malignancies. Blood 2002; 99: 75-82.
20. Feinstein L, Sandmaier B, Maloney D, McSweeney PA, Maris M, Flowers C, Radich J, Little MT, Nash RA, Chauncey T, Woolfrey A, Georges G, Kiem HP, Zaucha JM, Blume KG, Shizuru J, Niederwieser D, Storb R. Nonmyeloablative hematopoietic cell transplantation. Replacing high-dose cytotoxic therapy by the graft-versus-tumor effect. Ann N Y Acad Sci 2001; 938: 328-37.
21. Brandenburg U, Gottlieb D, Bradstock K. Antileukemic effects of rapid cyclosporin withdrawal in patients with relapsed chronic myeloid leukemia after allogeneic bone marrow transplantation. Leuk Lymphoma 1998; 31: 545-50.
22. Byrne JL, Stainer C, Hyde H, Miflin G, Haynes AP, Bessell EM, Russell NH. Low incidence of acute graft-versus-host disease and recurrent leukaemia in patients undergoing allogeneic haemopoietic stem cell transplantation from sibling donors with methotrexate and dose-monitored cyclosporin A prophylaxis. Bone Marrow Transplant 1998; 22: 541-5.
23. Dupuis LL, Taylor T, Saunders EF. Disposition of two oral formulations of cyclosporine in pediatric patients receiving hematopoietic stem cell transplants. Pharmacotherapy 2006; 26: 15-22.
24. Hendriks MP, Blijlevens NM, Schattenberg AV, Burger DM, Donnelly JP. Cyclosporine short infusion and C2 monitoring in haematopoietic stem cell transplant recipients. Bone Marrow Transplant 2006; 38: 521-5.
25. Jacobson PA, Ng J, Green KG, Rogosheske J, Brundage R. Posttransplant day significantly influences pharmacokinetics of cyclosporine after hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 2003; 9: 304-11.
26. Leather H, Boyette RM, Tian L, Wingard JR. Pharmacokinetic evaluation of the drug interaction between intravenous itraconazole and intravenous tacrolimus or intravenous cyclosporin A in allogeneic hematopoietic stem cell transplant recipients. Biol Blood Marrow Transplant 2006; 12: 325-34.
27. Parquet N, Reigneau O, Humbert H, Guignard M, Ribaud P, Socie G, Devergie A, Esperou H, Gluckman E. New oral formulation of cyclosporin A (Neoral) pharmacokinetics in allogeneic bone marrow transplant recipients. Bone Marrow Transplant 2000; 25: 965-8.
28. Schultz KR, Nevill TJ, Balshaw RF, Toze CL, Corr T, Currie CJ, Strong DK, Keown PA. Effect of gastrointestinal inflammation and age on the pharmacokinetics of oral microemulsion cyclosporin A in the first month after bone marrow transplantation. Bone Marrow Transplant 2000; 26: 545-51.
29. Hamwi A, Salomon A, Steinbrugger R, Fritzer-Szekeres M, Jager W, Szekeres T. Cyclosporine metabolism in patients after kidney, bone marrow, heart-lung, and liver transplantation in the early and late post transplant periods. Am J Clin Pathol 2000; 114: 536-43.
30. Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron 1976; Ref Type: Journal (Full) 16: 31-41.
31. D'Argenio D, Schumitzky A. ADAPT II User's Guide. Los Angeles: Biomedical Simulations Resource, 1997.
32. Beresini MH, Davalian D, Alexander S, Toton-Quinn R, Barnett B, Cerelli MJ, Hu MW, Berger DE, Blohm WP, Jaklitsch A. Evaluation of EMIT cyclosporine assay for use with whole blood. Clin Chem 1993; 39: 2235-41.
33. Hamwi A, Veitl M, Manner G, Ruzicka K, Schweiger C, Szekeres T. Evaluation of four automated methods for determination of whole blood cyclosporine concentrations. Am J Clin Pathol 1999; 112: 358-65.
34. Noem NO, Jelliffe RW. Modelling oral drug absorbtion as a cumulative Weibull function - use in a NPEM population model of cyclosporin. Ther Drug Monit 2001; 23: 493. Ref Type: Abstract
35. Rousseau A, Leger F, Le Meur Y, Saint-Marcoux F, Paintaud G, Buchler M, Marquet P. Population pharmacokinetic modeling of oral cyclosporin using NONMEM: comparison of absorption pharmacokinetic models and design of a Bayesian estimator. Ther Drug Monit 2004; 26: 23-30.
36. Holford NHG. Wings for NONMEM. Available at (last accessed 26 October 2011). 2007. Ref Type: Internet Communication.
37. Parke J, Holford NH, Charles BG. A procedure for generating bootstrap samples for the validation of nonlinear mixed-effects population models. Comput Methods Programs Biomed 1999; 59: 19-29.
38. Proost JH. Adaptive control of drug dosage regimens using maximum a posteriori probability Bayesian fitting. Int J Clin Pharmacol Ther 1995; 33: 531-6.
39. Sheiner LB, Beal SL. Some suggestions for measuring predictive performance. J Pharmacokinet Biopharm 1981; 9: 503-12.
40. Ingram D, Block R. Mathematical Methods in Medicine, Part 1. Statistical and Analytical Techniques. Chichester: John Wiley and Sons, 1984.
41. Oshima K, Kanda Y, Nakasone H, Arai S, Nishimoto N, Sato H, Watanabe T, Hosoya N, Izutsu K, Asai T, Hangaishi A, Motokura T, Chiba S, Kurokawal M. Decreased incidence of acute graft-versus-host disease by continuous infusion of cyclosporine with a higher target blood level. Am J Hematol 2008; 83: 226-32.
42. Schultz KR, Nevill TJ, Toze CL, Corr T, Currie C, Strong DK, Keown PA. The pharmacokinetics of oral cyclosporin A (Neoral) during the first month after bone marrow transplantation. Transplant Proc 1998; 30: 1668-70.
43. Serre-Debeauvais F, Iliadis A, Tranchand B, Michallet M, Benzekri S, Ardiet C, Cano JP, Hollard M, Gavend M. Bayesian estimation of cyclosporine clearance in bone marrow graft. Ther Drug Monit 1990; 12: 16-22.
44. Cremers S, Schoemaker R, Scholten E, den Hartigh J, Konig-Quartel J, van Kan E, Paul L, de Fijter J. Characterizing the role of enterohepatic recycling in the interactions between mycophenolate mofetil and calcineurin inhibitors in renal transplant patients by pharmacokinetic modelling. Br J Clin Pharmacol 2005; 60: 249-56.
45. Falck P, Midtvedt K, Van Le TT, Storehagen L, Holdaas H, Hartmann A, Asberg A. A population pharmacokinetic model of ciclosporin applicable for assisting dose management of kidney transplant recipients. Clin Pharmacokinet 2009; 48: 615-23.
46. Hesselink DA, van Gelder T, van Schaik RH, Balk AH, van HI, van Dam T, van der WM, Weimar W, Mathot RA. Population pharmacokinetics of cyclosporine in kidney and heart transplant recipients and the influence of ethnicity and genetic polymorphisms in the MDR-1, CYP3A4, and CYP3A5 genes. Clin Pharmacol Ther 2004; 76: 545-56.
47. Wu KH, Cui YM, Guo JF, Zhou Y, Zhai SD, Cui FD, Lu W. Population pharmacokinetics of cyclosporine in clinical renal transplant patients. Drug Metab Dispos 2005; 33: 1268-75.
48. Cantarovich M, Besner JG, Barkun JS, Elstein E, Loertscher R. Two-hour cyclosporine level determination is the appropriate tool to monitor Neoral therapy. Clin Transplant 1998; 12: 243-9.
49. Jaksch P, Kocher A, Neuhauser P, Sarahrudi K, Seweryn J, Wisser W, Klepetko W. Monitoring C2 level predicts exposure in maintenance lung transplant patients receiving the microemulsion formulation of cyclosporine (Neoral). J Heart Lung Transplant 2005; 24: 1076-80.
50. Mahalati K, Belitsky P, Sketris I, West K, Panek R. Neoral monitoring by simplified sparse sampling area under the concentration-time curve: its relationship to acute rejection and cyclosporine nephrotoxicity early after kidney transplantation. Transplantation 1999; 68: 55-62.
51. Cantarovich M, Elstein E, de Varennes B, Barkun JS. Clinical benefit of neoral dose monitoring with cyclosporine 2-hr post-dose levels compared with trough levels in stable heart transplant patients. Transplantation 1999; 68: 1839-42.
52. Levy G, Thervet E, Lake J, Uchida K. Patient management by Neoral C(2) monitoring: an international consensus statement. Transplantation 2002; 73: S12-S18.
53. Morton JM, Aboyoun CL, Malouf MA, Plit ML, Glanville AR. Enhanced clinical utility of de novo cyclosporine C2 monitoring after lung transplantation. J Heart Lung Transplant 2004; 23: 1035-9.
54. Nashan B, Cole E, Levy G, Thervet E. Clinical validation studies of Neoral C(2) monitoring: a review. Transplantation 2002; 73: S3-11.
55. Wacke R, Rohde B, Engel G, Kundt G, Hehl EM, Bast R, Seiter H, Drewelow B. Comparison of several approaches of therapeutic drug monitoring of cyclosporin A based on individual pharmacokinetics. Eur J Clin Pharmacol 2000; 56: 43-8.
56. Langers P, Cremers SC, den HJ, Rijnbeek EM, Ringers J, Lamers CB, Hommes DW, van HB. Individualized population pharmacokinetic model with limited sampling for cyclosporine monitoring after liver transplantation in clinical practice. Aliment Pharmacol Ther 2007; 26: 1447-54.
57. Cremers SC, Scholten EM, Schoemaker RC, Lentjes EG, Vermeij P, Paul LC, den Hartigh J, de Fijter JW. A compartmental pharmacokinetic model of cyclosporin and its predictive performance after Bayesian estimation in kidney and simultaneous pancreas-kidney transplant recipients. Nephrol Dial Transplant 2003; 18: 1201-8.
58. Langers P, Cremers SC, den Hartigh J, Rijnbeek EM, Ringers J, Lamers CB, van Hoek B. Easy-to-use, accurate and flexible individualized Bayesian limited sampling method without fixed time points for ciclosporin monitoring after liver transplantation. Aliment Pharmacol Ther 2005; 21: 549-57.
59. Wilhelm AJ, den Burger JC, Vos RM, Chahbouni A, Sinjewel A. Analysis of cyclosporin A in dried blood spots using liquid chromatography tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci 2009; 877: 1595-8.