The Use of Saliva in Therapeutic Drug Monitoring
The potential use of saliva in therapeutic drug monitoring cannot be assessed without an understanding of the nature of saliva and how it is collected, the diffusion of drugs across body membranes, and the determinants of a drug's eventual concentration in saliva. For several drugs, saliva concentration will suffice for the derivation of pharmacokinetic data and as an indication of compliance. However, in therapeutic drug monitoring stricter criteria must apply. The saliva concentration must be demonstrably related to drug response, or else reliably and predictably related to the free (unbound) concentration in plasma. Saliva concentrations are usually much lower than plasma concentrations, and quality control is particularly important to ensure accuracy and precision. If reliance is placed upon saliva measurements alone, no error is acceptable which could result in an incorrect therapeutic decision. Only phenytoin and carbamazepine can be considered suitable for therapeutic monitoring in saliva, and saliva sampling is likely to be of clinical value only where venepuncture is difficult or undesirable (e.g., in children), or where the protein binding of phenytoin is abnormal (e.g., renal failure, displacement interactions with other drugs).