Comparative pharmacokinetics after administration of a novel formulationof amphotericin B nanoparticles and amphotericin B deoxycholate to ratsand their antifungal activity in vitro
1School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China2Department of microbiology, Medical College of Chinese Peoples Armed Police Forces, Tianjin 300162, China
Abstract Purpose: To compare the pharmacokinetic characteristics in rats and the antifungal activity in vitro of a novel formulation of amphotericin B lipid nanoparticles (NS-AMB) with the commercial amphotericin B deoxycholate formulation (DAMB). Methods: Rats received a single intravenous injection of 1.0 mg NS-AMB or DAMB per kg. The plasma and tissue samples were obtained at indicated time intervals after dosing. The concentrations of amphotericin B in plasma and tissue samples were determined using high-pressure liquid chromatography and the pharmacokinetic parameters were calculated by a non-compartmental method. Results: After administration of NS-AMB to rats, significant accumulation of amphotericin B in the organs of the reticuloendothelial system (liver and spleen) was observed (P<0.01), however, the amphotericin B level in kidney, the major target organ for chronic amphotericin B toxicity, was significantly lower than that after administration of DAMB (P<0.01). NS-AMB achieved an 11-fold higher Cmax, a 10-fold greater AUC0-∞ in plasma and a smaller volume of distribution than DAMB. In the haematolysis studies, in contrast to DAMB, NS-AMB produced hardly any haematolysis. In addition, loading amphotericin B into nanoparticles had no inhibitory effect on its antifungal activity in vitro. Conclusion: The pharmacokinetics and tissue distribution properties of NS-AMB were strikingly different from those of DAMB. These results suggest that NS-AMB would be a good candidate for an amphotericin B formulation with low toxicity.
Li Yang,
Ping Xiao,
Caihong Shi etc
.Comparative pharmacokinetics after administration of a novel formulationof amphotericin B nanoparticles and amphotericin B deoxycholate to ratsand their antifungal activity in vitro[J] AJPS, 2007,V2(3): 122-129
2007, Vol. 2 