title: Comparison of trough, 2-hour, and limited AUC blood sampling for monitoring cyclosporin (Neoral) at day 7 post-renal transplantation and incidence of rejection in the first month.
abstract: The use of alternative strategies to the traditional pre-dose/trough (C0) blood sampling for cyclosporine (CsA) therapeutic drug monitoring has the potential to revolutionize analytical practices which have, in many centers, been established for some 20 years. While the C0 sample has previously been recommended, current attitudes are increasingly proposing alternatives for assessing CsA exposure, including various limited sampling strategies of the AUC (lssAUC) in the early postdose period, or alternative single-point nontrough samples, such as a 2-hour postdose sample (C2). The present study has reviewed a series of consecutive renal transplant recipients over 18 months where CsA was the primary immunosuppressant. The lssAUC performed at around day 7 posttransplantation included drawing blood at 0, 2, and 4 hours postdose, giving AUC(0-4). The aim of this study was to review the occurrence of acute biopsy-proven rejection in the first month and consider which of (simultaneously measured) C0, C2 or AUC(0-4) was a better early indicator of this adverse outcome. The result was best described by comparing the data from rejectors (n = 13) and nonrejectors (n = 42) for these 3 indices of CsA exposure (i.e., C0, C2 or AUC(0-4)). There was no evidence that C0 predicted the likelihood of such adverse clinical outcomes. In contrast, rejectors tended to have lower mean C2 CsA concentrations, and the incidence of rejection was 0.0 when C2 exceeded 1200 microg/L (n = 10). While the data are limited in the higher C2 CsA concentration range, it is nevertheless consistent with more recent recommendations suggesting that the CsA at C2 should target 1700 microg/L in this first month posttransplantation. As 64% of the patients were also receiving a CsA-sparing agent (diltiazem [DTZ]), the relationships were also investigated to determine whether any affect of concomitant DTZ therapy could be demonstrated. However, in this small sample, no significant affect of DTZ was seen.
authors.affiliation: Department of Cardiology & Clinical Pharmacology, The Queen Elizabeth Hospital, Woodville, South Australia. ray.morris@nwahs.sa.gov.au
authors.forename: Raymond G
authors.initials: RG
authors.lastname: Morris
authors.forename: Graeme R
authors.initials: GR
authors.lastname: Russ
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Cervelli
authors.forename: Rajiv
authors.initials: R
authors.lastname: Juneja
authors.forename: Stephen P
authors.initials: SP
authors.lastname: McDonald
authors.forename: Timothy H
authors.initials: TH
authors.lastname: Mathew
mesh_terms: D019540:Area Under Curve; D016572:Cyclosporine / Q000008:administration & dosage / Q000097:blood* / Q000627:therapeutic use; D016903:Drug Monitoring; D017248:Enzyme Multiplied Immunoassay Technique; D006084:Graft Rejection; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000097:blood* / Q000627:therapeutic use; D016030:Kidney Transplantation; D012189:Retrospective Studies; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine