SALIVARY EXCRETIOIN OF WARFARIN IN RABBITS : RELATIONSHIP BETWEEN PHARMACOLOGICAL EFFECT AND SALIVARY PHARMACOKINETICS OF WARFARIN IN RABBITS

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The salivary excretion of warfarin was investigated following intravenous and oral administration to rabbits. The salivary decay curves following intravenous injection (50 mg/kg) fitted to the two -compartment open model. On the other hand, following oral administration (100 mg/kg) the disposition of warfarin fitted to the one-compartment open model. There was a good linear relationship between the warfarin concentrations in saliva and plasma. The saliva vs. plasma (S/P) ratio was approximatelly 0.07. A good correlation was also observed between the warfarin concentrations in saliva and plasma protein-unbound fraction. The saliva vs. plasma protein-unbound fraction (S/P_f) ratio was approximatelly 0.92. Therefore, salivary concentration of warfarin corresponded with plasma free warfarin concentration. Furthermore, warfarin concentration in saliva was correlated with pharmacological effect, prothrombin complex activity. These results suggested that salivary warfarin concentration which was correlated with pharmacological effect had a possibility of utilization in pharmacokinetic studies and therapeutic drug monitoring.
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