NDLI: Safety and Toxicokinetics of Intravenous Liposomal Amphotericin B (AmBisome ®) in Beagle Dogs

Content Provider	Springer Nature Link
Author	Bekersky, Ihor Boswell, Garry W. Hiles, Richard Fielding, Robert M. Buell, Donald Walsh, Thomas J.
Copyright Year	1999
Abstract	Purpose. Amphotericin B (AmB) in small, unilamellar liposomes (AmBisome $^{®}$) has an improved therapeutic index, and altered pharmacokinetics. The repeat-dose safety and toxicokinetic profiles of AmBisome were studied at clinically relevant doses. Methods. Beagle dogs (5/sex/group) received intravenous AmBisome (0.25, 1,4, 8, and 16 mg/kg/day), empty liposomes or vehicle for 30 days. AmB was determined in plasma on days 1, 14, and 30, and in tissues on day 31. Safety parameters included body weight, clinical chemistry, hematology and microscopic pathology. Results. Seventeen of twenty animals receiving 8 and 16 mg/kg were sacrificed early due to weight loss caused by reduced food intake. Dose-dependent renal tubular nephrosis, and other effects characteristic of conventional AmB occurred at 1 mg/kg/day or higher. Although empty liposomes and AmBisome increased plasma cholesterol, no toxicities unique to AmBisome were revealed. Plasma ultrafiltrates contained no AmB. AmBisome achieved plasma levels 100-fold higher than other AmB formulations. AmBisome kinetics were non-linear, with clearance and distribution volumes decreasing with increasing dose. This, and nonlinear tissue uptake, suggest AmBisome disposition was saturable. Conclusions. AmBisome has the same toxic effects as conventional AmB, but they appear at much higher plasma exposures. AmBisome's non-linear pharmacokinetics are not associated with increased risk, as toxicity increases linearly with dosage. Dogs tolerated AmBisome with minimal to moderate changes in renal function at doses (4 mg/kg/day) producing peak plasma concentrations of 18−94 µg/mL.
Starting Page	1694
Ending Page	1701
Page Count	8
File Format	PDF
ISSN	07248741
Journal	Pharmaceutical Research
Volume Number	16
Issue Number	11
e-ISSN	1573904X
Language	English
Publisher	Kluwer Academic Publishers-Plenum Publishers
Publisher Date	1999-01-01
Publisher Place	New York
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Pharmacology/Toxicology Pharmacy Biochemistry Medical Law Biomedical Engineering
Content Type	Text
Resource Type	Article
Subject	Organic Chemistry Pharmacology Molecular Medicine Pharmacology (medical) Biotechnology Pharmaceutical Science

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

Safety, Toxicokinetics and Tissue Distribution of Long-Term Intravenous Liposomal Amphotericin B (ambisome®): A 91-day Study in Rats

Biodegradable Nanoparticles Improve Oral Bioavailability of Amphotericin B and Show Reduced Nephrotoxicity Compared to Intravenous Fungizone®

Dual Physiologically Based Pharmacokinetic Model of Liposomal and Nonliposomal Amphotericin B Disposition

The care and feeding of a commercial liposomal product: liposomal amphotericin B $(AmBisome^{®}$)

Antifungal Efficacy of an Intravenous Formulation Containing Monomeric Amphotericin B, 5-Fluorocytosine, and Saline for Sodium Supplementation

Intratracheal Versus Intravenous Liposomal Delivery of siRNA, Antisense Oligonucleotides and Anticancer Drug

Block Copolymer Micelles for the Encapsulation and Delivery of Amphotericin B

Poor and Unusually Prolonged Oral Absorption of Amphotericin B in Rats

Encapsulation and Release of Amphotericin B from an ABC Triblock Fluorous Copolymer

Safety and Toxicokinetics of Intravenous Liposomal Amphotericin B (AmBisome ®) in Beagle Dogs

Similar Documents

Safety, Toxicokinetics and Tissue Distribution of Long-Term Intravenous Liposomal Amphotericin B (ambisome®): A 91-day Study in Rats

Biodegradable Nanoparticles Improve Oral Bioavailability of Amphotericin B and Show Reduced Nephrotoxicity Compared to Intravenous Fungizone®

Dual Physiologically Based Pharmacokinetic Model of Liposomal and Nonliposomal Amphotericin B Disposition

The care and feeding of a commercial liposomal product: liposomal amphotericin B $(AmBisome^{®}$)

Antifungal Efficacy of an Intravenous Formulation Containing Monomeric Amphotericin B, 5-Fluorocytosine, and Saline for Sodium Supplementation

Intratracheal Versus Intravenous Liposomal Delivery of siRNA, Antisense Oligonucleotides and Anticancer Drug

Block Copolymer Micelles for the Encapsulation and Delivery of Amphotericin B

Poor and Unusually Prolonged Oral Absorption of Amphotericin B in Rats

Encapsulation and Release of Amphotericin B from an ABC Triblock Fluorous Copolymer

Safety and Toxicokinetics of Intravenous Liposomal Amphotericin B (AmBisome ®) in Beagle Dogs