Influence of saliva pH-value on the ratio of amphetamine saliva to serum concentration

Introduction:

In child and adolescent psychiatry, measurement of drug concentrations in saliva may be an interesting non-invasive alternative to therapeutic drug monitoring (TDM) in blood. However, therapeutic and dose-related reference ranges are defined only for blood samples. The aim of this study is to assess the correlation between amphetamine concentration in saliva and serum and to determine the influence of pH on the amphetamine saliva-to-serum ratio.

Methods:

28 patients (aged 7.4 – 16.9 years, ♂ = 23 ♀ = 5) with attention-deficit/hyperactivity disorder treated with dexamphetamine or lisdexamphetamine, a prodrug of amphetamine, were included. Blood and saliva samples were collected simultaneously at the time of maximum serum concentration of amphetamine. The ratio of saliva/serum concentration was calculated to analyze the drug distribution in relation to saliva pH. Due to the exponential relationship between saliva/serum concentration ratio and saliva pH the ratio was logarithmized for linear testing by Spearman rank correlation (ρ).

Results:

A mean linear relationship between saliva and serum concentration (ρ= 0.628, p < 0.001) was found. Using logarithmized ratios of saliva/serum concentrations an inverse linear correlation with saliva pH (ρ=-0.712, p < 0.001) was observed.

Conclusion:

Our findings demonstrate that the pH-value is an important modifier of the salivary amphetamine concentration. It is known that the salivary flow rate highly influences the pH of oral fluid, e.g. hyposalivation reduces the physiological buffer capacity of saliva. On the other hand, hypersalivation stabilizes and increases salivary pH in oral fluid by higher secretion rate of bicarbonate. Moreover, medication or psychological factors e.g. stress or anxiety can cause hyposalivation and decrease salivary pH. Future studies are needed to systematically investigate influencing factors on pH-values such as saliva flow rate.