Therapeutic drug concentration monitoring using saliva samples. Focus on anticonvulsants.

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.