Cyclophosphamide pharmacokinetics in mice: a comparison between retro orbital sampling versus serial tail vein bleeding

R Said, M Abdel-Rehim, B Sadeghi… - The open …, 2007 - benthamopen.com
R Said, M Abdel-Rehim, B Sadeghi, S Al-Hashemi, Z Hassan, M Hassan
The open pharmacology journal, 2007benthamopen.com
Preclinical studies on pharmacokinetics in animals usually require at least 3-5 animals per
time point. The use of several animals in each time point may increase the result variation
due to individual dosing errors and inter-and intraindividual variation among animals.
Moreover, a large number of animals has to be euthanized in these experiments. In the
present paper, the pharmacokinetics of the anticancer drug, cyclophosphamide was
investigated using serial bleeding from the tail vein and compared with the kinetics obtained …
Abstract
Preclinical studies on pharmacokinetics in animals usually require at least 3-5 animals per time point. The use of several animals in each time point may increase the result variation due to individual dosing errors and inter-and intraindividual variation among animals. Moreover, a large number of animals has to be euthanized in these experiments. In the present paper, the pharmacokinetics of the anticancer drug, cyclophosphamide was investigated using serial bleeding from the tail vein and compared with the kinetics obtained from traditional retro-orbital sinus bleeding in mice. Cyclophosphamide (100 mg/kg) was administered intraperitoneally to two groups of mice. Blood samples were collected at 0, 0.25, 0.5, 1, 2, 3, 4, 5 and 6 hr. In the first group (n= 6), 20 µL blood samples were collected from the tail-vein by serial bleeding. In the second group, 3 animals were killed at each time point and blood was collected from both tail vein and retro-orbital sinus. Cyclophosphamide analysis in whole blood was carried out using LC-MS/MS with on-line sample preparation utilizing microextraction by packed sorbent (MEPS). Pharmacokinetics including AUC, tmax, Cmax and half–life were estimated using WinNonLin.
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