Modelling ciclosporin double-peak absorption profiles in the early post-transplantation period.
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.
Rousseau
Annick
A
Department of Pharmacology and Toxicology, University Hospital Dupuytren, 2 Avenue Martin-Luther-King, F-87042 Limoges Cedex, France.
Marquet
Pierre
P
D000042:Absorption; D016572:Cyclosporine / Q000493:pharmacokinetics*; D006801:Humans; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics*; D016030:Kidney Transplantation; D008954:Models, Biological
D007166:Immunosuppressive Agents; D016572:Cyclosporine