After administering an oral dose of monofluorophosphate (MFP) to human beings or rats, a fraction of the drug appears in plasma that is bound to proteins, establishing a previously undetected compartment of nondiffusible fluoride. This article documents experiments performed in vitro, describing the binding of MFP to two plasma globulins: alpha2-macroglobulin and C3 (a beta-globulin). MFP binds irreversibly to these proteins through a stable bond. MFP binds to purified alpha2-macroglobulin or to C3 with a molar ratio MFP: protein close to unity. MFP binding reduces significantly the biological activity of these proteins, which share in common a macrocyclic 4-residue ring thiolactone (Cys-Gly-Glu-Glu). The binding site of MFP is as yet unknown. Protein-bound MFP appeared in the plasma of volunteers during the 5-7 hours following intake. Peak concentration of protein-bound MFP and maximal reduction of alpha2-macroglobulin activity was observed 2 hours after intake. Clearance of protein-bound MFP coincided with the return of alpha2-macroglobulin to basal levels.

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The administration of 1,25-dihydroxycholecalciferol to rats increased their calciuresis as a power function of the dose. Up to 95% of the urinary calcium was excreted as a non-ionized complex, together with equimolar amounts of citrate. The stoichiometry between calcium and citrate, observed at all dose levels, suggests that citrate metabolism is coordinated with the mobilization of calcium.

Pharmacological doses of estradiol administered to rats increased the Ca mass of their femurs through a significant reduction in the rate of Ca resorption. On a body basis, the same animals showed increased rates of skeletal Ca deposition and resorption and no effect on the skeletal mass. The non uniform effect of estradiol on the skeleton, if confirmed in the human being, may limit the applicability of estrogenic treatment.

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