Application of a Volumetric Absorptive Microsampling Device to a Pharmacokinetic Study of Tacrolimus in Rats: Comparison with Wet Blood and Plasma.


Drug Metabolism and Pharmacokinetics, Eisai Co., Ltd, Tokodai 5-1-3, Tsukuba-shi, Ibaraki, 300-2635, Japan. [Email]


OBJECTIVE : Volumetric absorptive microsampling (VAMS) devices are useful for sampling a smaller volume of blood from rodents in the preclinical setting. In the present study, we evaluated the proof of concept of a VAMS device by comparing the pharmacokinetic data of tacrolimus in rats among dried blood in VAMS, wet blood, and plasma.
METHODS : Tacrolimus was administered orally, to rats, at a dose of 10 mg/kg. Only 10 μL aliquots of blood were absorbed by VAMS devices at designated time points. Tacrolimus was extracted with a methanol-water mixture (1:1, v/v) via sonication. Tacrolimus levels in wet blood (10 μL) and plasma (10 μL) were quantified after protein precipitation.
RESULTS : Tacrolimus in VAMS devices was quantifiable from 0.2 ng/mL using high-performance liquid chromatography with tandem mass spectrometer. Accuracy and precision were within the acceptance criteria. Bland-Altman plots showed that tacrolimus concentrations in VAMS devices were similar to those in wet blood, regardless of tacrolimus levels. On the other hand, tacrolimus levels in plasma were different from those in VAMS devices, especially at lower concentrations, likely due to partition of tacrolimus to blood cells. However, pharmacokinetic parameters were comparable among the three matrices.
CONCLUSIONS : Collectively, these findings suggest that the VAMS device can be a useful device for pharmacokinetic studies in rats.