Liu H, Delgado M R
Department of Research, Texas Scottish Rite Hospital for Children, Dallas, USA.
Clin Pharmacokinet. 1999 Jun;36(6):453-70. doi: 10.2165/00003088-199936060-00006.
In the last 30 years there has been great interest in the use of saliva in therapeutic drug monitoring. Numerous investigators have suggested that saliva be used as an alternative body fluid for the therapeutic drug monitoring of anticonvulsant drugs. Not only can saliva be obtained easily on multiple occasions with minimal discomfort to the patient but, more importantly, useful relationships exist between the saliva and blood concentrations of the most commonly used anticonvulsant drugs. The measurement of anticonvulsant drug concentrations in saliva has been applied to pharmacokinetic and pharmacodynamic studies, and for therapeutic drug monitoring in a variety of seizure disorders. However, this simple and non-invasive method is not widely accepted in clinical practice. Several recent developments in sample collection and analytical methods, and the growing interest in free drug concentrations, provide a renewed impetus for saliva sampling for therapeutic drug monitoring of anticonvulsant drugs. Salivary flow rates vary significantly both between individuals and under different conditions. The use of stimulated saliva has several advantages over resting saliva. The salivary flow rate and pH, sampling conditions, contamination and many other pathophysiological factors may influence the concentrations of the medication in saliva. However, under standardised and well-controlled sampling condition, therapeutic drug monitoring of anticonvulsant drugs in saliva can be useful for determining compliance with medication in paediatric patients, for analysing the concentration of free drug and in situations where repeated sampling is necessary. Saliva is an alternative matrix for the therapeutic drug monitoring of carbamazepine, phenytoin, primidone and ethosuximide because the concentrations of these medications in saliva reflect the concentrations of the drug in serum. This is not the case for valproic acid (valproate sodium) and some controversy exists for phenobarbital. Further studies are required to assess the clinical value of monitoring anticonvulsant drugs and their metabolites in saliva, to examine the influence of pathophysiological factors on salivary drug concentrations, to improve the design of special devices to reproducibly and conveniently collect saliva samples, and to develop and use new analytical methods to achieve more sensitive and accurate results.
在过去30年里，唾液在治疗药物监测中的应用引起了极大关注。众多研究人员建议将唾液用作抗惊厥药物治疗药物监测的替代体液。唾液不仅可以在多次采集时轻松获取，对患者造成的不适最小，而且更重要的是，最常用抗惊厥药物的唾液浓度与血液浓度之间存在有用的关系。唾液中抗惊厥药物浓度的测量已应用于药代动力学和药效学研究，以及各种癫痫发作疾病的治疗药物监测。然而，这种简单且非侵入性的方法在临床实践中并未被广泛接受。样本采集和分析方法的一些最新进展，以及对游离药物浓度的兴趣日益增加，为唾液采样用于抗惊厥药物的治疗药物监测提供了新的动力。个体之间以及在不同条件下，唾液流速差异很大。与静息唾液相比，使用刺激唾液有几个优点。唾液流速和pH值、采样条件、污染以及许多其他病理生理因素可能会影响唾液中药物的浓度。然而，在标准化且控制良好的采样条件下，唾液中抗惊厥药物的治疗药物监测对于确定儿科患者的用药依从性、分析游离药物浓度以及在需要重复采样的情况下可能是有用的。唾液是卡马西平、苯妥英、扑米酮和乙琥胺治疗药物监测的替代基质，因为这些药物在唾液中的浓度反映了血清中药物的浓度。丙戊酸（丙戊酸钠）并非如此，苯巴比妥存在一些争议。需要进一步研究来评估监测唾液中抗惊厥药物及其代谢物的临床价值，研究病理生理因素对唾液药物浓度的影响，改进特殊装置的设计以可重复且方便地采集唾液样本，并开发和使用新的分析方法以获得更灵敏和准确的结果。
