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 sal iva be used as an alternative body fluid for the therapeutic drug monitorin g of anticonvulsant drugs. Not only can saliva be obtained easily on multip le occasions with minimal discomfort to the patient but, more importantly, useful relationships exist between the saliva and blood concentrations of t he most commonly used anticonvulsant drugs. The measurement of anticonvulsant drug concentrations in saliva has been ap plied to pharmacokinetic and pharmacodynamic studies, and for therapeutic d rug monitoring in a variety of seizure disorders. However, this simple and noninvasive method is not widely accepted in clinical practice. Several rec ent developments in sample collection and analytical methods, and the growi ng interest in free drug concentrations, provide a renewed impetus for sali va sampling for therapeutic drug monitoring of anticonvulsant drugs. Salivary flow rates vary significantly both between individuals and under d ifferent conditions. The use of stimulated saliva has several advantages ov er resting saliva. The salivary flow rate and pH, sampling conditions, cont amination and many other pathophysiological factors may influence the conce ntrations of the medication in saliva. However, under standardised and well -controlled sampling condition, therapeutic drug monitoring of anticonvulsa nt drugs in saliva can be useful for determining compliance with medication in paediatric patients, for analysing the concentration of free drug and i n situations where repeated sampling is necessary. Saliva is an alternative matrix for the therapeutic drug monitoring of carb amazepine, phenytoin, primidone and ethosuximide because the concentrations of these medications in saliva reflect the concentrations of the drug in s erum. This is not the case for valproic acid (valproate sodium) and some co ntroversy 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 saliv ary drug concentrations, to improve the design of special devices to reprod ucibly and conveniently collect saliva samples, and to develop and use new analytical methods to achieve more sensitive and accurate results.