Abstract
Cyclosporin A (CsA) absorption is variable in bone marrow transplant (BMT) patients compromising the efficacy of graft-versus-host disease prevention. Neoral, a new microemulsion formulation of CsA which has an improved bioavailibility, increases intestinal absorption of the drug with less variable pharmacokinetic parameters in non-BMT patients. In order to predict the best dosage of Neoral when patients are switched from i.v. to oral administration we performed a randomised study comparing two oral doses, either the same or twice the last i.v. dose used after BMT. Fourteen adults were randomised around day 25 after BMT. Whole blood CSA concentrations were measured 2 and 12 h after the oral administration of Neoral on days 0, 7 and 14 to determine residual and maximum concentration, and modified whenever necessary to maintain blood level CsA concentration within therapeutic range (150–250 ng/ml). We found that patients who received twice the last i.v. dose had better concentrations than patients from the other group while toxicity was identical in both groups. We conclude that doubling the last i.v. dose during the switch to oral administration of Neoral gives the best therapeutic range concentration and should be recommended for graft-versus-host prevention. Bone Marrow Transplantation (2000) 25, 965–968.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Holt DW, Mueller EA, Kovarik JM et al. The pharmacokinetics of Sandimmun Neoral: a new oral formulation of cyclosporine Transplant Proc 1994 26: 2935–2939
Holt DW, Johnson A . Cyclosporine microemulsion Biodrugs 1997 7: 175–197
Sullivan KM, Shulman HM, Storb R et al. Chronic graft-versus-host disease in 52 patients: adverse natural course andsuccessful treatment with combination immunosuppression Blood 1981 57: 267–276
Cole E, Keown P, Landsberg D et al. Safety and tolerability of cyclosporine and cyclosporine microemulsion during 18 months of follow-up in stable renal transplant recipients Transplantation 1988 65: 505–510
Thomas ED, Storb R, Clift RA et al. Bone marrow transplantation New Engl J Med 1975 292: 832–843, 895–902
Yee GC . Pharmacokinetic and pharmacodynamic studies of cyclosporine in bone marrow transplantation Transplant Proc 1990 22: 1327–1330
Humbert H . Variabilité de la biodisponibilité de la ciclosporine: avantage de la formulation Néoral Thérapie 1996 52: 353–357
Atkinson K . Cyclosporin in bone marrow transplantation Bone Marrow Transplant 1987 1: 265–270
Yee G, McGuire T, Honaker M et al. Serum cyclosporin concentration and risk of acute graft-versus-host disease after allogeneic bone marrow transplantation New Engl J Med 1988 319: 65–70
Calne RY, White DJG, Thiru S et al. Cyclosporin A in patients receiving renal allografts from cadaver donors Lancet 1978 II: 1323–1327
Gratwohl A, Speck B, Wenk M et al. Cyclosporine in human bone marrow transplantation. Serum concentration, graft-versus-host disease, and nephrotoxicity Transplantation 1983 36: 40–44
Feutren G, Wong R, Jin J et al. Safety and tolerability of Neoral in transplant recipients Transplant Proc 1996 4: 2177–2182
Primmett DRN, Levine M, Kovarik JM et al. Cyclosporine monitoring in patients with renal transplants: two- or three-point methods that estimate area under the curve are superior to through levels in predicting drug exposure Therapeutic Drug Monitor 1998 20: 276–283
Friman S, Bäckman L . A new microemulsion formulation of cyclosporin. Pharmacokinetic and clinical features Clin Pharmacokinet 1996 30: 181–193
Frei UA, Neumayer HH, Buchholz B et al. Randomised, double-blind, one-year study of the safety and tolerability of cyclosporine microemulsion compared with conventional cyclosporine in renal transplant patients Transplantation 1998 65: 1455–1460
Storb R, Deeg H, Whitehead J et al. Methotrexate and cyclosporin compared with cyclosporin alone for prophylaxis of acute graft-versus-host disease after bone marrow transplantation for leukemia New Engl J Med 1986 314: 729–735
Schultz KR, Nevill TJ, Toze CL et al. The pharmacokinetics of oral cyclosporine A (Neoral) during the first month after bone marrow transplantation (BMT) Blood 1997 90: (Suppl.1) 375B
McGuire TR, Honaker M, Lynch JC et al. Renal dysfunction associated with cyclophosphamide (CSA) prophylaxis in HLA matched sibling peripheral blood stem cell transplantation (AlloBSCT): conversion from intravenous CSA to a new oral formulation Blood 1999 94: (Suppl.1) 334a
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Parquet, N., Reigneau, O., Humbert, H. et al. New oral formulation of cyclosporin A (Neoral) pharmacokinetics in allogeneic bone marrow transplant recipients. Bone Marrow Transplant 25, 965–968 (2000). https://doi.org/10.1038/sj.bmt.1702375
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.bmt.1702375
Keywords
This article is cited by
-
A decision support tool to find the best cyclosporine dose when switching from intravenous to oral route in pediatric stem cell transplant patients
European Journal of Clinical Pharmacology (2020)
-
Converting cyclosporine A from intravenous to oral administration in hematopoietic stem cell transplant recipients and the role of azole antifungals
European Journal of Clinical Pharmacology (2018)
-
Pharmacokinetics of CsA during the switch from continuous intravenous infusion to oral administration after allogeneic hematopoietic stem cell transplantation
Bone Marrow Transplantation (2010)
-
The impact of cyclosporin A on acute graft-versus-host disease after allogeneic bone marrow transplantation in children and adolescents with acute lymphoblastic leukemia
Bone Marrow Transplantation (2005)