Pharmacokinetics of multivesicular liposomal encapsulated cytarabine when administered subcutaneously in dogs.
J Vet Intern Med
; 34(4): 1563-1569, 2020 Jul.
Article
em En
| MEDLINE
| ID: mdl-32442344
ABSTRACT
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:
To perform a LC pharmacokinetic (PK) study when administered SC in dogs. ANIMALS Five healthy female beagles.METHODS:
Three-period, 3-treatment, nonblinded, randomized, and crossover design, including a pilot study. LC was administered at 50 mg/m2 SC and FC was administered at 25 and 50 mg/m2 SC and IV. Plasma CA concentrations were measured until 240, 72, and 8 hours after SC LC, SC FC, and IV FC administration, respectively. CA plasma concentrations were quantitated by ultra-high-performance liquid chromatography with mass spectrometry (MS/MS) detection and concentration-time profiles were evaluated by noncompartmental analysis.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 In healthy dogs, SC LC administration at 50 mg/m2 results in measurable plasma CA concentrations, is apparently safe and well tolerated, but does not result in prolonged cytotoxic plasma concentrations. Poor absorption of LC prevented establishment of a complete LC PK profile.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Citarabina
/
Cães
/
Lipossomos
/
Antimetabólitos Antineoplásicos
Limite:
Animals
Idioma:
En
Revista:
J Vet Intern Med
Assunto da revista:
MEDICINA INTERNA
/
MEDICINA VETERINARIA
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Estados Unidos