Comparison of the effects of liposomal amphotericin B and conventional amphotericin B on propafenone metabolism and hepatic cytochrome P-450 in rats

The effects of conventional amphotericin B (AmB) dissolved in sodium deoxyc holate on microsomal cytochrome P-450 concentrations and propafenone metabo lism to 5-hydroxy-propafenone and N-desalkyl-propafenone were compared with those of liposomal AMB (Li-AMB) in rats. AmB (3 mg/kg/day, intravenously [ i.v.]) given for 4 days caused a significant decrease in the concentration of hepatic microsomal cytochrome P-450 (0.43 +/- 0.06 nmol/mg versus 0.62 /- 0.05 nmol/mg for the control [P < 0.05]), Following the application of L i-AMB (15 mg/kg/day, i.v.), hepatic microsomal cytochrome P-450 concentrati ons were unchanged at 0.64 +/- 0.08 nmol/mg, AmB decreased ex vivo propafen one metabolism to 5-hydroxy-propafenone and N-desalkyl-propafenone signific antly. Sodium deoxycholate (the vehicle of AmB) by itself induced a signifi cant decline of 5-hydroxy-propafenone and N-desalkyl-propafenone production , while microsomal cytochrome P-450 concentrations remained unchanged, In c ontrast, LI-AMB did not change the levels of production of 5-hydroxy-propaf enone or of N-desalkyl-propafenone at either substrate concentration tested (50 mu mol and 200 mu mol). Microsomal AmB concentrations were significant ly higher following Li-AMB application (21.1 +/- 6.2 mu g/g versus 3.7 +/- 1.4 mu g/g for AmB [P < 0.05]), We conclude that Li-AMB, in contrast to AmB , decreases neither hepatic microsomal cytochrome P-450 nor hepatic propafe none metabolism in rats ex vivo. Sodium deoxycholate alone decreases propaf enone metabolism in a similar way to AmB, suggesting that it participates i n AmB-induced disturbance of hepatic metabolic function.