Comparison of the pharmacokinetic profiles of two different amphotericin B formulations in healthy dogs

Abstract

This study was conducted to compare the pharmacokinetic profiles of conventional Liposomal amphotericin B showed markedly higher peak plasma concentrations (approximately ninefold greater) and higher area under the plasma concentration curve values (approximately 14-fold higher) compared to conventional formulation. It is concluded that AmBisome ® reached higher plasma concentration and lower distribution volume and had a longer half-life compared to Fungizone ® , and therefore, AmBisome ® is reported to be an appropriate and effective choice for the treatment of systemic mycotic infections in dogs.

Incidence of acute kidney injury in dogs with systemic mycotic infections treated with amphotericin B (1996‐2020)

“…Labrador retrievers and German shepherd dogs were over-represented relative to the general population of dogs that presented during this time frame. Fungal diagnoses included coccidioidomycosis (14), aspergillosis (9), cryptococcosis (8), hyalohyphomycosis (5), Rasamsonia piperina Of the 51 dogs, 12 (24%) received AmB-D and 39 (76%) dogs received ABLC. Six of the 51 dogs received subsequent courses of therapy but only data from the first treatment course is included.…”

“…9 Other lipid-based formulations such as liposomal amphotericin B (AmBisome, Astella Pharma, Northbrook, IL) have superior safety profiles to even ABLC; however, veterinary use is limited because of cost. 5,14 Limited data are available assessing the risk of kidney injury in clinical cohorts of dogs receiving AmB to treat systemic mycoses and factors that might increase the odds of developing an AKI. In one clinical trial that included 11 dogs with blastomycoses treated with ABLC, AKI was not reported.…”

“…Conventional AmB is complexed with sodium deoxycholate (AmB‐D; Fungizone, Xediton Pharmaceuticals Inc., Ontario, CA). It can cause cytotoxicosis to the distal renal tubules and potentially vasoconstriction that alters renal blood flow, leading to an increased risk of acute kidney injury (AKI) 5‐7 . To minimize nephrotoxicosis, AmB‐D is generally administered to dogs three times weekly, spaced at least 48 hours apart, as a 1 to 2 hour infusion with IV fluid diuresis 8,9 .…”

“…In people, there is a reduction in mean serum creatinine (Cr) in patients receiving ABLC, 11 and ABLC does not significantly affect serum Cr in people with pre‐existing renal disease 9 . Other lipid‐based formulations such as liposomal amphotericin B (AmBisome, Astella Pharma, Northbrook, IL) have superior safety profiles to even ABLC; however, veterinary use is limited because of cost 5,14 …”

“…It can cause cytotoxicosis to the distal renal tubules and potentially vasoconstriction that alters renal blood flow, leading to an increased risk of acute kidney injury (AKI). 5 , 6 , 7 To minimize nephrotoxicosis, AmB‐D is generally administered to dogs three times weekly, spaced at least 48 hours apart, as a 1 to 2 hour infusion with IV fluid diuresis. 8 , 9 Newer, lipid‐based amphotericin B formulations have a superior safety profile and have largely replaced the use of AmB‐D in people.…”