Therapeutic drug monitoring of digoxin in Jordanian patients: Comparing saliva versus plasma

Abstract

Therapeutic drug monitoring (TDM) is measuring drug concentrations in plasma, serum or blood, to assure that drug concentrations can be maintained within a target range and to make sure the amount of medicine being administered is both safe and effective. TDM is essential to avoid digoxin toxicity due to its narrow therapeutic window (therapeutic levels of digoxin are 0.8-2.0 ng/mL. The toxic level is >2.4 ng/mL). TDM of digoxin is currently performed by plasma sampling, which is an invasive and painful procedure. The aim of the study is to study the pharmacokinetics of digoxin in plasma and saliva matrices in hospitalized human volunteers; to suggest using non-invasive saliva sampling instead of plasma in monitoring drug’s level. Plasma and saliva samples were collected for 20 patients. Plasma and saliva concentrations were determined by validated liquid chromatography mass spectrometry. Excel was used to determine the pharmacokinetics parameters, pbpk modeling was performed using PKSim version 10. Blood and saliva samples were collected from patients prior to taking each dose of digoxin and after; to compare plasma and saliva levels. As a result there was a significant strong correlation between saliva and plasma peak and trough concentrations. There was a significant relationship between gender (p-value 0.01) , weight (p-value 0.013), albumin (p-value 0.008), alanine transaminase (p-value 0.009)and aspartate transaminase (p-value 0.009) with digoxin salivary peak concentration. Creatinine had a strong correlation with saliva AUC values (r =0.5785, p = 0.008).To conclude saliva can be used as an alternative for plasma in monitoring digoxin’s levels. This is the first study in digoxin therapeutic drug monitoring using saliva and physiologically based pharmacokinetic modeling.

Keywords

• Salivary excretion classification system
• therapeutic drug monitoring
• digoxin
• correlation of concentration with biochemical parameters
• pk-sim
• saliva/plasma ratio of digoxin

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