| Abstrakt: |
Phase 0 clinical studies, which are known as microdose trials, are expected to promote drug development and reduce development costs. The accelerator mass spectrometry (AMS) system is expected to play an important role in the microdosing tests, as it is a highly sensitive measurement system that can be used to determine the drug concentrations in these tests. Using the AMS system, we measured the background 14C-concentration in human blood and evaluated the data for use as a reference in microdose studies that administer 14C-labeled compounds in humans. Blood samples of five healthy Japanese volunteers (three men, two women, median age 40.4 ± 9.8 years) were collected around the same time and just prior to when the subjects ate a meal (between 12:00 noon and 2:00 pm). Centrifugal separations of blood that was allowed to clot and the plasma were performed at 503 g for 2 min at 4°C. Background 14C-concentration for each of the samples was measured using the AMS system. The Institute of Accelerator Analysis, which is the first contract research organization in Japan that is capable of providing AMS analysis services for carbon dating and bioanalysis work, performed the AMS analysis. The mean 14C-concentration in blood was 1.613 ± 0.125 dpm/ml (men 1.668 ± 0.114 dpm/ml, women 1.514 ± 0.076 dpm/ml), in clots 2.373 ± 0.087 dpm/ml (men 2.381 ± 0.101 dpm/ml, women 2.357 ± 0.060 dpm/ ml), and in plasma 0.648 ± 0.049 dpm/ml (men 0.647 ± 0.059 dpm/ml, women 0.649 ± 0.032 dpm/ml). The coefficient variation (CV) for blood was 7.8% (men 6.9%, women 5.0%), for clots 3.7% (men 4.3%, women 2.5%), and for plasma 7.6% (men 9.1%, women 4.9%). The 14C-concentrations of the clot and blood were higher than those of plasma. The 14C-concentrations in the blood and plasma were slightly different between individuals when compared with the values for the clot, although the differences were quite small, with a CV value less than 7.8%. Even though the 14C-concentration differed only slightly between individuals, 14C-concentrations of the clot and blood were higher than those of the plasma. Therefore, the variation and difference of the background data for blood and plasma might be of use as a reference for microdosing test evaluations. [ABSTRACT FROM AUTHOR] |
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