Pharmacokinetic profile of intravenous liposomal triamcinolone acetonide in the rabbit.

The pharmacokinetics of triamcinolone [2-14C]acetonide, encapsulated in neutral multilamellar liposomes, and a control preparation of the steroid in a 3:1 solution of polyethylene glycol-water was investigated in the rabbit after single intravenous bolus injections. Blood samples were obtained at various times up to 7 hr postinjection and assayed for the drug by liquid scintillation counting. Blood drug concentration-time data showed biexponential decay and were analyzed by nonlinear, least-squares regression analysis to obtain the initial (time zero) drug concentration [(Cb)0] and the initial (fast, alpha) and terminal (slow, beta) disposition rate constants. From these estimates the central compartment volume (Vc) and the respective half-lives [(t1/2) alpha, (t1/2) beta] of the fast and slow disposition phases were calculated. The total body clearance (CLT) and the apparent distribution volume (Vd) were obtained by nonparametric analysis. Significant differences were observed between the liposome-encapsulated dosage form and the solution of the steroid in beta and Vd beta. While beta for the liposomal form was smaller than that for the solution, the apparent Vd was larger with the liposome-encapsulated drug. There was no difference in the total body clearance of the drug in the two dosage forms. Results of the study suggest that when administered by the intravenous route, liposome-encapsulated drug may exhibit extensive tissue distribution and a prolonged half-life.