Tsiropoulos I, Kristensen O, Klitgaard N A
Department of Neurology, Odense University Hospital, Denmark.
Ther Drug Monit. 2000 Oct;22(5):517-21. doi: 10.1097/00007691-200010000-00003.
The authors examined the interindividual correlation between saliva and serum concentrations of lamotrigine (LTG) and the relationship between LTG concentration in saliva and the free LTG concentration in serum in 40 patients with epilepsy, aged 16 to 73 years, receiving stable doses of LTG and comedication. Saliva was collected before and after stimulation of salivary flow. The free LTG fraction was determined by equilibrium dialysis and ultrafiltration. Drug analysis was performed by high-performance liquid chromatography. The correlation between LTG daily dose and serum concentration was weak but significant (r = 0.47). There was high correlation between LTG concentration in serum and unstimulated (r = 0.85) or stimulated (r = 0.94) saliva, and between total LTG concentration in serum and the free LTG fraction as determined by ultrafiltration (r = 0.95) and equilibrium dialysis (r = 0.93). Lamotrigine concentration in stimulated saliva was significantly correlated to the free LTG fraction. Protein binding of LTG calculated from concentration in stimulated saliva, as determined by ultrafiltration and equilibrium dialysis, was 51.8% +/- 13.03%, 68.05% +/- 7.59%, and 58.72% +/- 7.68% (mean +/- standard deviation) respectively. The differences between the three methods were significant. The authors conclude that saliva sampling may be a useful alternative to blood tests for monitoring LTG treatment.
作者研究了40例年龄在16至73岁、接受稳定剂量拉莫三嗪(LTG)及联合用药的癫痫患者唾液与血清中拉莫三嗪浓度的个体间相关性,以及唾液中LTG浓度与血清中游离LTG浓度的关系。在刺激唾液分泌前后收集唾液。通过平衡透析和超滤法测定游离LTG分数。采用高效液相色谱法进行药物分析。LTG日剂量与血清浓度之间的相关性较弱但具有显著性(r = 0.47)。血清中LTG浓度与未刺激(r = 0.85)或刺激后(r = 0.94)唾液中的LTG浓度之间,以及血清中总LTG浓度与通过超滤法(r = 0.95)和平衡透析法(r = 0.93)测定的游离LTG分数之间存在高度相关性。刺激后唾液中的拉莫三嗪浓度与游离LTG分数显著相关。通过超滤法和平衡透析法测定,由刺激后唾液浓度计算得出的LTG蛋白结合率分别为51.8%±13.03%、68.05%±7.59%和58.72%±7.68%(均值±标准差)。三种方法之间的差异具有显著性。作者得出结论,唾液采样可能是监测LTG治疗的一种有用的替代血液检测的方法。