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

Introduction:

In child and adolescents 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 only defined for blood. The aim of this ongoing 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:

Participants were patients with attention-deficit/hyperactivity disorder (aged 6 – 18) treated with dexamphetamine or lisdexamphetamine, a prodrug of amphetamine. 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 analyse the drug distribution in these matrices over a saliva pH range. Due to the exponential relationship between saliva/serum concentration ratio and saliva pH the ratio was logarithmised for linear testing by Spearman rank correlation (ρ).

Fig. 1: Relationship between the logarithmised amphetamine saliva to serum concentration ratio at the time of maximum serum concentration and the saliva pH for n = 14 participants treated with lisdexamphetamine.

Results:

Preliminary results of 14 patients revealed no significant relationship between saliva and serum concentration (ρ= 0.279, p = 0.334). In contrast, the logarithmised ratios of saliva/serum concentrations showed a significant inverse linear correlation with saliva pH (ρ=-0.653, p = 0.011; Fig. 1).

Discussion:

The pH-value is an important modifier of the salivary amphetamine concentration. Future studies need to further investigate the correlation of saliva and peripheral blood concentrations of psychopharmacolocgical substances, in order to determine the usefulness of saliva measurements for TDM.