title: CsA 2-h concentration correlates best with area under the concentration-time curve after allo-SCT compared with trough CsA.
abstract: The relationship between CsA levels and area under the curve (AUC) in allo-SCT recipients, and the effect of age, concomitant use of steroid and MDR-1 polymorphism on this relationship remain largely unexplored. Steady-state CsA blood concentrations at time 0 (C0), 1 (C1), 1.5 (C1.5), 2 (C2), 3 (C3), 4 (C4), 6 (C6), 8 (C8) and 12 (C12) h post oral CsA dose were taken from 27 consenting allo-SCT recipients (receiving myeloablative or non-myeloablative conditioning) at D(15)-D(25) (all participants) and D(40)-D(80) (participants with myeloablative conditioning). The CsA AUC(0-4h), AUC(0-8h) and AUC(0-12h) were determined using trapezoidal rule, and the relationships between AUCs and CsA concentrations at various time points were examined. Poor correlation was observed between C0 and AUC(0-4h) (r(2)=0.15), AUC(0-8h) (r(2)=0.21) and AUC(0-12h) (r(2)=0.53). C2 was better correlated with AUC(0-4h) (r(2)=0.88), AUC(0-8h) (r(2)=0.76) and AUC(0-12h) (r(2)=0.83). The aforementioned factors did not influence the observed relationship. CsA levels taken at 2 h post oral CsA administration may represent the optimal time point for monitoring the biological effects of calcineurin inhibitors in allo-SCT recipients.
authors.affiliation: Department of Pharmacy Practice, Centre for Medicine Use and Safety, Faculty of Pharmacy and Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia.
authors.forename: D C M
authors.initials: DC
authors.lastname: Kong
authors.forename: P
authors.initials: P
authors.lastname: Shuttleworth
authors.forename: M
authors.initials: M
authors.lastname: Bailey
authors.forename: A
authors.initials: A
authors.lastname: Grigg
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics; D000293:Adolescent; D000328:Adult; D019540:Area Under Curve; D016572:Cyclosporine / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006086:Graft vs Host Disease / Q000235:genetics / Q000401:mortality / Q000517:prevention & control*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D033581:Stem Cell Transplantation; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D007166:Immunosuppressive Agents; D016572:Cyclosporine