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Cyclosporin twice or three times daily dosing in pediatric transplant patients – It is not the same!
Author(s) -
Filler Guido,
De Barros Viviane Rocha,
Jagger Justin E,
Christians Uwe
Publication year - 2006
Publication title -
pediatric transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.457
H-Index - 69
eISSN - 1399-3046
pISSN - 1397-3142
DOI - 10.1111/j.1399-3046.2006.00592.x
Subject(s) - medicine , dosing , cyclosporins , intensive care medicine , pediatrics , transplantation
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 × h × kg/mL × mg (range: 1253–4319) on b.i.d. to 1016 ng × h × kg/mL × 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.