ORAL-ADMINISTRATION OF LIPOSOMES CONTAINING CYCLOSPORINE - A PHARMACOKINETIC STUDY

Liposomal formulation containing cyclosporine A (CSA) were prepared. T he most stable liposomes with the composition of CSA, dipalmitoylphosp hatidyl choline (DPPC) and cholesterol (Chol.) in molar ratio 1:0.2:1, respectively were administered orally to New Zealand rabbits. The pha rmacokinetic of the administered CSA was compared with that of the com mercially available oily oral formulation of CSA (Sandimmune) at dose of 15 mg/kg. Cyclosporine concentration in blood was monitored using a radioimmunoassay method (RIA). A change in the pharmacokinetic parame ters of CSA due to liposomal encapsulation was observed. A peak concen tration was reached in 50 min in case of liposomes compared with 225 m in in case of Sandimmune. The rate of absorption (C(max)AUC(0-infinity )) was significantly faster following the liposome administration. A s ignificant difference in the area under the concentration curve (AUC(0 -infinity)) was found and this was attributed to the difference in the terminal half-lives (t(1/2)beta) which were 8.88 +/- 1.94 and 19.3 +/ - 8.48 h for liposomes and Sandimmune preparations, respectively. The mean residence time (MRT) and the mean absorption time (MAT) were dram atically decreased following the administration of liposomal formulati on. Generally, there was less inter-individual variation in the values of rate of absorption, t(1/2)beta and MRT when CSA liposomes were ora lly administered compared to the administration of Sandimmune. Thus, a n oral liposomal formulation for CSA can be developed to offer the adv antages of low variability and fast onset of action. (C) 1998 Elsevier Science B.V. All rights reserved.