title: Cyclosporin twice or three times daily dosing in pediatric transplant patients - it is not the same!
abstract: Not infrequently, physicians elect to divide CyA-ME from b.i.d. to t.i.d. dosing in an effort to minimize toxicity. Equivalent exposure is assumed. Few studies have compared 24-h PK profiles on both dosing regimes in the same patient. We retrospectively studied a heterogeneous population of seven pediatric patients (one heart transplant, five renal transplants and one FSGS patient) on both dosing regimes who had complete 24-h PK profiles on CyA-ME. Four patients were converted from b.i.d. to t.i.d. and three patients from t.i.d. to b.i.d. dosing. There was no difference in the dose/kg (5.66 +/- 2.52 mg/kg on b.i.d. dosing and 5.75 +/- 1.81 mg/kg on t.i.d. dosing, p = 0.8578, two-sided t-test). When comparing the dose-normalized AUCs over 24 h, every single patient demonstrated lower CyA-ME exposure on t.i.d. than on b.i.d. dosing with an average relative bioavailability that was 37.9% lower on t.i.d. than on b.i.d. dosing. The median dose-normalized AUC(0-->24h) dropped from 1620 ng x h x kg/mL x mg (range: 1253-4319) on b.i.d. to 1016 ng x h x kg/mL x mg (range: 712-1485, p = 0.02, Wilcoxon's matched pairs test) on t.i.d. dosing. Our results indicate t.i.d. dosing of CyA-ME results in significantly lower exposure when the same total dose is administered in two divided doses. This reduced exposure may potentially increase the risk for rejection.
authors.affiliation: Department of Pediatrics, Children's Hospital of Eastern Ontario, University of Ottawa, Ottawa, ON, Canada. filler@cheo.on.ca
authors.forename: Guido
authors.initials: G
authors.lastname: Filler
authors.forename: Viviane Rocha
authors.initials: VR
authors.lastname: de Barros
authors.forename: Justin E
authors.initials: JE
authors.lastname: Jagger
authors.forename: Uwe
authors.initials: U
authors.lastname: Christians
mesh_terms: D000293:Adolescent; D019540:Area Under Curve; D002648:Child; D016572:Cyclosporine / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005923:Glomerulosclerosis, Focal Segmental / Q000188:drug therapy*; D016027:Heart Transplantation; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D016030:Kidney Transplantation; D008297:Male; D012189:Retrospective Studies
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine