PHARMACOKINETICS OF DIFFERENT FLUORINATED SUBSTANCES AND PHARMACEUTICAL PREPARATIONS

Abstract

Sodium fluoride (NaF) and disodium monofluorophosphate (MFP) are compounds containing fluoride extensively studied in their actions and metabolism. After an oral dose of NaF, fluoride is absorbed in stomach and intestine. In blood, fluoride is not bound to proteins and is cleared by kidneys and bones. In calcified tissues, fluoride replaces the hydroxyl of hydroxyapatite to form fluorapatite. MFP has better gastric tolerance and co-administration with calcium does not hinder their bioavailability. However, there are more differences between NaF and MFP. After an oral dose, MFP is absorbed through gastric and duodenal mucosa and binds to plasma alfa-2-macroglobulin. The protein is inactivated by the binding and the complex is cleared from plasma by receptors located in bone and liver. The complex is accumulated in bone matrix and is then metabolized to lower molecular weight peptides, and finally to fluoride. The described metabolism enlarges the half-life of fluoride in the body and it is probably the cause of its sustained effect on bone mass.