Pharmacokinetics of multivesicular liposomal encapsulated cytarabine when administered subcutaneously in dogs.
DepoCyt
canine
chemotherapy
cytarabine
cytosar
leukemia
lymphoma
meningoencephalomyelitis of unknown etiology
pharmacokinetics
Journal
Journal of veterinary internal medicine
ISSN: 1939-1676
Titre abrégé: J Vet Intern Med
Pays: United States
ID NLM: 8708660
Informations de publication
Date de publication:
Jul 2020
Jul 2020
Historique:
received:
22
10
2019
revised:
23
04
2020
accepted:
06
05
2020
pubmed:
23
5
2020
medline:
11
3
2021
entrez:
23
5
2020
Statut:
ppublish
Résumé
Prolonged cytotoxic concentrations of cytarabine (CA) are required for maximum cytotoxicity. DepoCyt is a human liposomal cytarabine (LC) product that lasts longer in plasma and CSF compared with free CA (FC). The use of LC has not been evaluated in dogs. To perform a LC pharmacokinetic (PK) study when administered SC in dogs. Five healthy female beagles. Three-period, 3-treatment, nonblinded, randomized, and crossover design, including a pilot study. LC was administered at 50 mg/m Subcutaneous LC administration resulted in a maximum plasma concentration of 26.3 to 59.78 ng/mL, time to reach maximum plasma concentration of 2 hours, area under the concentration-time curve to last measurable concentration of 669.3 to 1126 h × ng/mL, and plasma bioavailability (%F) of 19.6% to 31.3%. The PK profiles of FC after SC and IV administration differed when compared with LC. In healthy dogs, SC LC administration at 50 mg/m
Sections du résumé
BACKGROUND
BACKGROUND
Prolonged cytotoxic concentrations of cytarabine (CA) are required for maximum cytotoxicity. DepoCyt is a human liposomal cytarabine (LC) product that lasts longer in plasma and CSF compared with free CA (FC). The use of LC has not been evaluated in dogs.
OBJECTIVES
OBJECTIVE
To perform a LC pharmacokinetic (PK) study when administered SC in dogs.
ANIMALS
METHODS
Five healthy female beagles.
METHODS
METHODS
Three-period, 3-treatment, nonblinded, randomized, and crossover design, including a pilot study. LC was administered at 50 mg/m
RESULTS
RESULTS
Subcutaneous LC administration resulted in a maximum plasma concentration of 26.3 to 59.78 ng/mL, time to reach maximum plasma concentration of 2 hours, area under the concentration-time curve to last measurable concentration of 669.3 to 1126 h × ng/mL, and plasma bioavailability (%F) of 19.6% to 31.3%. The PK profiles of FC after SC and IV administration differed when compared with LC.
CONCLUSIONS AND CLINICAL IMPORTANCE
CONCLUSIONS
In healthy dogs, SC LC administration at 50 mg/m
Identifiants
pubmed: 32442344
doi: 10.1111/jvim.15809
pmc: PMC7379012
doi:
Substances chimiques
Antimetabolites, Antineoplastic
0
Liposomes
0
Cytarabine
04079A1RDZ
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1563-1569Subventions
Organisme : Department of Clinical Sciences at Auburn University College of Veterinary Medicine
Informations de copyright
© 2020 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.
Références
Vet Comp Oncol. 2018 Mar;16(1):E1-E15
pubmed: 29027350
Cancer Chemother Pharmacol. 1991;29(1):13-8
pubmed: 1742843
Ann Pharmacother. 2000 Oct;34(10):1173-8
pubmed: 11054987
Clin Pharmacokinet. 2002;41(10):705-18
pubmed: 12162758
Vet Rec. 2013 May 18;172(20):527
pubmed: 23462382
J Small Anim Pract. 2010 Mar;51(3):138-49
pubmed: 19814766
J Vet Intern Med. 2006 Sep-Oct;20(5):1178-83
pubmed: 17063713
J Biol Chem. 1980 Oct 10;255(19):8997-900
pubmed: 7410404
Cancer Res. 1993 Apr 1;53(7):1596-8
pubmed: 8453629
J Vet Pharmacol Ther. 2018 Oct;41(5):638-643
pubmed: 29761906
Bioanalysis. 2011 Jul;3(14):1603-11
pubmed: 21756093
J Vet Intern Med. 2020 Jul;34(4):1563-1569
pubmed: 32442344
Vet Comp Oncol. 2008 Jun;6(2):80-9
pubmed: 19178667
J Small Anim Pract. 2006 Oct;47(10):588-95
pubmed: 17004951
Clin Pharmacokinet. 2006;45(12):1153-76
pubmed: 17112293
Vet J. 2010 Jun;184(3):290-7
pubmed: 19410487
J Vet Pharmacol Ther. 2013 Aug;36(4):408-11
pubmed: 22943060
Pharmacol Rev. 2016 Jul;68(3):701-87
pubmed: 27363439
Vet J. 2011 Apr;188(1):34-8
pubmed: 20627636
Cancer Treat Rep. 1987 May;71(5):447-50
pubmed: 3567968
Vet Comp Oncol. 2016 Dec;14(4):417-446
pubmed: 28530307
Cancer Res. 1987 Aug 1;47(15):3935-7
pubmed: 3607740