Lee M G, Chen M L, Huang S M, Chiou W L
Biopharm Drug Dispos. 1981 Jan-Mar;2(1):89-97. doi: 10.1002/bdd.2510020110.
Distribution kinetics of gentamicin in whole blood were studied. After spiking human blood to an initial concentration of 20 microgram ml-1, plasma gentamicin concentrations dropped to minima at about 5 min then increased to maxima at about 15 min and remained constant afterwards. A difference of up to 36 per cent between the maximum and minimum was found. The equilibration was faster with lower initial concentrations. These unusual distribution phenomena might be attributed to the Schiff base formation between nonprotonated amino groups of gentamicin and free fatty aldehyde groups on blood cell membrane. The mean equilibrium blood cells/plasma partition ratio was about 0.1. Similar equilibration kinetics were observed with blood of rabbits after being intravenously dosed with gentamicin. Therefore, the time elapsed between the collection and centrifugation of blood samples, especially shortly after dosing, may have a significant effect on the 'measured' plasma gentamicin concentration. Distribution between plasma and blood cells may also occur in a similar manner with other drugs which have primary amino groups. It is recommended that distribution kinetics of drugs and metabolites in blood be included in pharmacokinetic studies.
研究了庆大霉素在全血中的分布动力学。将人血加样至初始浓度为20微克/毫升后，血浆庆大霉素浓度在约5分钟时降至最低，然后在约15分钟时升至最高，此后保持恒定。发现最高值与最低值之间相差高达36%。初始浓度较低时平衡更快。这些不寻常的分布现象可能归因于庆大霉素的非质子化氨基与细胞膜上的游离脂肪醛基团之间形成席夫碱。平均平衡血细胞/血浆分配比约为0.1。给兔子静脉注射庆大霉素后，在其血液中观察到了类似的平衡动力学。因此，血液样本采集与离心之间的时间间隔，尤其是给药后不久，可能会对“测得的”血浆庆大霉素浓度产生显著影响。血浆和血细胞之间的分布也可能以类似方式发生在其他含有伯氨基的药物中。建议将药物及其代谢物在血液中的分布动力学纳入药代动力学研究。
