Monitoring of warfarin therapy: Preliminary results from a longitudinal pilot study

The aim of this study was to investigate the relationship between warfarin dosage, international normalized ratio, plasma and oral fluid concentrations of warfarin, and its metabolites, namely RR/SS- and RS/SR-warfarin alcohols. Nine patients on long-term warfarin therapy (4 with stable and 5 with unstable international normalized ratio values) were longitudinally monitored for over two months by recording warfarin dosage and measuring international normalized ratio, warfarin and warfarin alcohols concentrations in oral fluid and in plasma. At equivalent dose (20–30 mgweek–1), the international normalized ratio was in the range 2.0–2.5 and 1.5–3.1 for stable and unstable patients, respectively. Moreover, stable patients showed nearly double total and unbound plasma warfarin concentration, and nearly triple oral fluid warfarin concentrations compared to unstable patients. Correlations between warfarin dosage and total plasma concentration of warfarin (r = 0.65, p <0.01) or RS/SR-warfarin alcohols (r = 0.66, p <0.01), as well as between stimulated oral fluid and total plasma concentrations of warfarin (r = 0.72, p <0.01) and RS/SR-warfarin alcohols (r = 0.95, p <0.01) suggest that the relative changes of the oral fluid concentrations of these species may provide clinically useful information for monitoring individual patients. Follow-up data revealed that even in the absence of changes of warfarin dose, the oscillations of plasma and oral fluid of WAR and RS/SR-warfarin alcohols parallel oscillations of international normalized ratio. Due to the long delay of its biological action, monitoring the plasma concentration of warfarin might help to predict variations of international normalized ratio and prevent the risk of thrombotic or haemorrhagic events. The information collected suggests that non-invasive monitoring of warfarin in oral fluid might represent a suitable tool for this purpose.