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The concentration of diazepam in the plasma and saliva of 9 normal human subjects receiving a single oral dose of diazepam (10 mg) over an 8-hr The secretion of drugs into saliva has been the subject of many investigations in man. [2][3][4][5][6]11 Both parotid saliva and mixed saliva have been used to evaluate the usefulness of this biologic fluid in predicting blood concentrations of drugs. The exchange of drugs between blood and saliva is determined by many variables, including protein binding, degree of lipid solubility, extent of ionization, and molecular size of the particular drug.Diazepam is a long-acting lipophilic drug, primarily undissociated at physiologic pH, which has a high affinity for plasma proteins,9 The remaining nonprotein bound (free) form of this drug distributes widely throughout the body, particularly into the central nervous system, The free form of diazepam in the central nervous system has been quantitated in human cerebrospinal fluid.9 Little or no information, however, has been published on the availability of the free form (unbound) of diazepam in human salivary secretions.

Doxorubicin and 5-fluorouracil pharmacokinetics were studied in 19 volunteers with various advanced neoplastic diseases who received 50-90 mg doxorubicin or 600-1000 mg 5-fluorouracil intravenously, followed by plasma and parotid saliva collection over a 75 min period. The extent to which these chemotherapeutic agents are bound to plasma proteins, at concentrations chosen to approximate plasma concentrations, was measured by equilibrium dialysis. Both agents were quantitated by high-performance liquid chromatography. As reported previously, a wide range of plasma levels were found among patients receiving similar doses of either doxorubicin or 5-fluorouracil. It appears that in addition to being quickly cleared from the plasma both chemotherapeutic agents are excreted in detectable amounts in parotid saliva, a route of elimination heretofore given little or no attention. Excretion in the saliva exposes the mucosa of the upper gastrointestinal tract to 5-fluorouracil after intravenous administration and may play a part in causing stomatitis in patients receiving it by this route. Since there are huge interindividual and pronounced intraindividual differences in S/P ratios mostly not systematically related to the drugs' concentration in plasma, the concentration in parotid saliva was not useful in predicting the level of free doxorubicin or 5-fluorouracil in plasma.