The pharmacokinetics of cytarabine administered subcutaneously, combined with prednisone, in dogs with meningoencephalomyelitis of unknown etiology

被引:12
作者
Pastina, B. [1 ]
Early, P. J. [1 ]
Bergman, R. L. [2 ]
Nettifee, J. [1 ]
Maller, A. [3 ]
Bray, K. Y. [4 ]
Waldron, R. J. [5 ]
Castel, A. M. [6 ]
Munana, K. R. [1 ]
Papich, M. G. [1 ]
Messenger, K. M. [1 ]
机构
[1] North Carolina State Univ, Coll Vet Med, Raleigh, NC 27695 USA
[2] Carolina Vet Specialists, Matthews, NC USA
[3] Madison Vet Specialists, Madison, WI USA
[4] Carolina Vet Specialists, Winston Salem, NC USA
[5] Upstate Vet Specialist, Greenville, SC USA
[6] Univ Tennessee, Coll Vet Med, Vet Teaching Hosp C247, Knoxville, TN USA
关键词
canine; cytarabine; MUE; Pharmacokinetics; sparse sampling; subcutaneous; pharmacokinetics; CYTOSINE-ARABINOSIDE; INFUSION; ORIGIN;
D O I
10.1111/jvp.12667
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The objective of this study was to describe the pharmacokinetics (PK) of cytarabine (CA) after subcutaneous (SC) administration to dogs with meningoencephalomyelitis of unknown etiology (MUE). Twelve dogs received a single SC dose of CA at 50mg/m(2) as part of treatment of MUE. A sparse sampling technique was used to collect four blood samples from each dog from 0 to 360min after administration. All dogs were concurrently receiving prednisone (0.5-2mgkg(-1)day(-1)). Plasma CA concentrations were measured by HPLC, and pharmacokinetic parameters were estimated using nonlinear mixed-effects modeling (NLME). Plasma drug concentrations ranged from 0.05 to 2.8g/ml. The population estimate (CV%) for elimination half-life and Tmax of cytarabine in dogs was 1.09 (21.93) hr and 0.55 (51.03) hr, respectively. The volume of distribution per fraction absorbed was 976.31 (10.85%) ml/kg. Mean plasma concentration of CA for all dogs was above 1.0g/ml at the 30-, 60-, 90-, and 120-min time points. In this study, the pharmacokinetics of CA in dogs with MUE after a single 50mg/m(2) SC injection in dogs was similar to what has been previously reported in healthy beagles; there was moderate variability in the population estimates in this clinical population of dogs.
引用
收藏
页码:638 / 643
页数:6
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