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Modelling ciclosporin double-peak absorption profiles in the early post-transplantation period
Annick Rousseau1, Pierre Marquet
1Department of Pharmacology and Toxicology, University Hospital Dupuytren, 2 Avenue Martin-Luther-King, F-87042 Limoges Cedex, France.
Objective:
To apply a recent double-peak absorption model to ciclosporin.
Methods:
Pharmacokinetic evaluation was performed in 20 patients who had undergone de novo renal transplantation and were receiving immunosuppressive therapy with corticosteroids, mycophenolate mofetil and ciclosporin Neoral. Data were analysed by nonlinear mixed-effects modelling using individual and population approaches.
Results:
Six patients presented pharmacokinetic profiles with two peaks, whereas 14 curves apparently had a single, sometimes delayed and wide, peak. A one-compartment model with first-order elimination in association with the double-peak absorption model best fitted the data. This model reliably described the pharmacokinetics of ciclosporin, whether or not a double peak was present on the concentration-time profiles.
Conclusions:
The double-peak absorption model could be useful to optimise ciclosporin exposure in the early post-transplantation period.
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