Effect of co-administration of Intralipid on the pharmacokinetics of cyclosporine in the rabbit.

The effect of Intralipid co-administration on the pharmacokinetics of cyclosporine (CyA) was studied in NZW rabbits. A single intravenous bolus dose of CyA (10 mg kg-1) mixed with 3 ml of Intralipid was administered to rabbits (n = 4). Control animals (n = 4) received the same dose of CyA without Intralipid. Serial blood samples were collected up to 12 h after the administration of CyA. Concentrations of CyA in plasma were analyzed using a HPLC method. The terminal elimination half-life (t1/2) of CyA was significantly lower with Intralipid administration (191 +/- 25 min) than control (298 +/- 59 min). The total body clearance (ClTOT) and volume of distribution (Vdss) of CyA was reduced by approximately 65-70 per cent with Intralipid administration compared to control. The free fraction of CyA in plasma with and without Intralipid administration was estimated to be 0.05 +/- 0.01 and 0.17 +/- 0.06, respectively. Co-administration of Intralipid with CyA decreased both the ClTOT and Vdss resulting in a rapid elimination, i.e., decrease in a t1/2 of CyA from the body.