The Pharmacokinetics and Pharmacodynamics of Intravenous Uricase Multivesicular Liposomes

Objective To determine and compare the pharmacokinetics and pharmacodynamics of uricase-multivesicular liposomes (UOMVLs) with free uricase (UOX) in rats. Methods UOMVLs were prepared by the double emulsion method and confirmed with its entrapment efficiency, size and Zeta potential. Twelve healthy rats were randomly divided into two groups: one with i.v. injection of UOMVLs, and the other with i.v. injection of UOX. Their serum activity of uricase was assayed. The pharmacokinetic parameters were calculated using software DAS 2.1.1. Another 24 male SD rats were enrolled, the rat model of hyperuricemia was established with hypoxanthine and potassium oxonate, while normal group (n=6) was set as control. Injection of UOMVLs (1 mL, 0.47 U/mL), UOX (1 mL, 0.47 U/mL) and nothiy were given 1 h later in UOMVLs group (n=6), UOX group (n=6) and model group (n=6), and their serum uric acid levels were determined 1, 2, 3, 5, 7, 9, 12, 24, 36, 48 h after the establishment of hyperuricemia model. Results The entrapment efficiency of UOMVLs was (63.75 ± 3.65)%, with an average particle size of (22.56 ± 1.70) μm and Zeta potential of (-41.81±6.59) mV. The pharmacokinetic parameters of UOMVLs and UOX were as follows, respectively: area under time-concentration curve from 0 to infinity time (AUC0-∞) (498.83±58.85) U/L·h and (28.49±9.95) U/L·h; time to peak concentration (tmax) (1.00±0.00) h and (0.00±0.00) h; peak concentration (Cmax) (73.04±6.35) U/L and (31.00±6.03) U/L; elimination half-life (t1/2) (3.49±0.80) h and (1.17±0.33) h. The relative bioavailability of UOMVLs was (1 750.90±206.56) %. UOMVLs decreased serum uric to normal in 9 h; whereas it took 48 h for the UOX group and the model group to return to normal. Conclusion UOMVLs can prolong tmax and t1/2 and improve the relative bioavailability. UOMVLs decrease serum uric acid levels in rats with hyperuricemia more effectively than UOX.