The Use of Oral Fluid for Therapeutic Drug Management

Abstract

One of the underlying tenets of clinical pharmacology is that only free drugs are pharmacologically active. It is thought that only free drugs can cross biological membranes to interact with a given receptor to alter its function, and that drug responses, both efficacious and toxic, are a function of unbound concentrations. The rationale for measuring drugs in oral fluid is that the free fraction of a drug in plasma reaches equilibrium with the drug in saliva. Although reports concerning the appearance of organic solutes in saliva have been in the literature for over 70 years, it has only been in the past 30 years that there has been emphasis on the appearance of drugs. Although many assumptions for drug level monitoring in saliva are made, the primary requisite for salivary monitoring to be useful is a constant or predictable relationship between the drug concentration in saliva and the drug concentration in plasma. Measurement of oral fluid drug levels for the purpose of managing patients and making dosage adjustments may be useful for select drugs or drug classes. However, it does not appear to be useful for the majority of drugs therapeutically monitored. Some work with antipsychotic medications has indicated that although the measurement of drug concentrations themselves may not be useful for dosage adjustment, the ratio of parent drug to metabolite may reflect altered metabolic status due to either pharmacogenetic variation or other clinical conditions. Furthermore, analysis of saliva may provide a cost-effective approach for the screening of large populations.

A Comparison of Intranasal and Oral Scopolamine for Motion Sickness Prevention in Military Personnel

“…Bioavailability studies have shown that when dealing with acidic medications, quite often equilibrium favors blood and not saliva and that some medications have rate limiting steps during absorption which limits movement to the oral fluid (Langman, 2007). The intranasal scopolamine formulation used in this study was acidic (pH=3.5 and pKa=7.55 @ 23°C) potentially making saliva absorption values less accurate and reliable.…”

“…It is hypothesized that these results could be due to the use of salivary assays rather than plasma for reporting scopolamine levels. According to researchers in the field of biochemistry and pharmacology, the primary requisite for use of salivary assays for evaluating the bioavailability of medication is a constant or predictable relationship between the drug concentration in saliva and the drug concentration in plasma (Fatah & Cohen, 2003;Haeckel, 1993;Jusko & Milsap, 1993;Langman, 2007;Margel & Schulz, 2007). Jusko and Milsap (1993) state that the utility of salivary assays for pharmacokinetic and pharmacodynamic studies relies on a drug that exhibits a constant saliva/plasma ratio that is independent of drug concentration, is resistant to changes in salivary flow, and is consistent among individuals.…”

Alternative Sampling Strategies for Cytochrome P450 Phenotyping

“…For example, as concentrations in oral fluid reflect the free, non-protein bound, pharmacologically active fraction of a drug in plasma, oral fluid sampling has gained attention as a tool for therapeutic monitoring of selected drugs [67]. Currently, the best established applications of oral fluid are probably roadside and workplace drug testing [68,69].…”

Opening the toolbox of alternative sampling strategies in clinical routine: A key-role for (LC-)MS/MS

“…Moreover, even when a correlation is observed, the latter might be time-or concentration dependent and/or intra-and interpatient variability may be too large to allow reliable use in clinical practice 17 . Therefore, oral fluid is probably not suitable for TDM of most therapeutic drugs 96 . Generally, non-ionizable drugs (at least within the pH range of oral fluid) are considered the best candidates 10,16 .…”