To prove the clinical usefulness of cortisol measurements in saliva for the exact assessment of a patient's corticoid status under therapeutic hormone substitution, we measured simultaneously total cortisol in serum and non-protein-bound cortisol in saliva after administration of different forms of hydrocortisone (cortisol) in eight cortisol-suppressed, healthy male volunteers. The intravenous and oral administration of 20 mg of cortisol exceeds the binding capacity of the corticosteroid-binding globulin (CBG), leading to an increase of the ratio between salivary and serum cortisol at the higher cortisol concentrations in blood. After rectal administration of 100 mg of cortisol acetate, the serum cortisol concentration does not exceed the binding capacity of CBG, so the ratio between salivary and serum cortisol remains nearly constant. However, this ratio was higher after rectal administration than after intravenous and oral administration, probably because of weaker binding of the acetate form of cortisol to CBG. Thus, the salivary measurement of the non-protein-bound (i.e., biologically active) cortisol offers a convenient way to monitor the effectiveness of various forms of systemic corticoid substitution.
AIDS encephalopathy is an insidious complication of human immunodeficiency virus infection which is difficult to treat because of the poor uptake of many potentially useful antiretroviral drugs through the blood-brain barrier. A chemical delivery system (CDS) for zidovudine (AZT) based on redox trapping within the brain has been prepared and tested in several animal models to circumvent this limitation. The behavior of the AZT-CDS in the dog was considered. Parenteral administration of AZT resulted in rapid systemic elimination and poor uptake by the central nervous system. Ratios of the area under the concentration-time curve of AZT for cerebrospinal fluid to that for blood were 0.32, and ratios of the area under the concentration-time curve of AZT for brain to that for blood were approximately 0.25. Administration of an aqueous formulation of the AZT-CDS resulted in rapid tissue uptake and conversion of the CDS to the corresponding quaternary salt with the subsequent production of AZT. Delivered in this way, the levels of AZT in brain were 1.75- to 3.3-fold higher than those associated with conventional AZT administration. In addition, the levels of AZT in blood were 46% lower than those associated with AZT administration. The higher concentrations in brain and lower concentration in blood combined to significantly increase the ratio of the concentration of AZT in the brain to that in blood after AZT-CDS administration compared to that after AZT dosing.
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