A rapid, sensitive, and specific liquid chromatography method for the simultaneous determination of four protease inhibitors (indinavir, nelfinavir, ritonavir, and saquinavir) in human plasma is described. After a liquid-liquid extraction with terbutyl methyl ether and a sequential washing of the reconstituted sample with hexane, protease inhibitors are separated on a phenyl column using a simple binary mobile phase of ammonium acetate buffer:acetonitrile (48:52) (pH = 7.5) with an ultraviolet detection at 260 nm. The standard curves are linear in the range 0.025-1 microg/mL for saquinavir, 0.1-4 microg/mL for indinavir and nelfinavir, and 0.25-10 microg/mL for ritonavir, with an average recovery ranging from 79% to 99%, and with both low interday and intraday coefficients of variation (<15%). This assay is simple, rapid (15-minute interval between runs) , and useful for therapeutic monitoring of the protease inhibitors on a routine basis.

Inflammatory processes may be suppressed by endogenous mechanisms such as release of adrenocorticosteroid hormones through stimulation of the hypothalamus-pituitary-adrenal axis. In the present study, the relationship between the temporal development of carrageenan-induced edema in the hindlimb of the rat and release in plasma of the principal endogenous adrenocorticosteroid of the rat corticosterone was investigated. Suplantar injection of carrageenan produced a biphasic increase in basal plasma corticosterone levels that was not attributed to diurnal variation. The plasma level of corticosterone increased rapidly after injection of carrageenan and peaked 12-fold at 20 min. This first phase increase was attributed to the stress of the injection since it was mimicked by subplantar injection of saline. The second phase of corticosterone release was gradual and peaked 12-fold 7 hr after injection of carrageenan. The second phase was not elicited by subplantar injection of saline. When the hypothalamus-pituitary-adrenal axis is impaired via hypophysectomy, carrageenan-induced edema is more intense and lasts longer than in control rats. The results demonstrate that adrenocorticosteroid hormones are released as a result of the stress of injection and by the inflammatory response. Release of adrenocorticosteroids acts as a feedback mechanism to suppress the inflammatory response.

351 SPF OF1 non-immunized mice of both sexes were infected by aerosolized Pasteurella multocida. Female mice were significantly less susceptible to infection than were males of the same age (which were heavier). Males and females of equal bodyweight, but different age, showed no significant difference in susceptibility. The difference at equal ages can be explained by the lower respiratory flow of females. The consequences of these results for experimental studies on atmospheric pollutants are discussed.

The kinetics of amphotericin B (AMB) concentrations in plasma and interstitial fluid were studied in an experimental model of Candida albicans infection in rabbits. Rabbits were infected by subcutaneously implanted fibrin clots containing the yeast. Three groups of five rabbits received a 4 mg kg-1 AMB infusion. AMB (Fungizone) was dissolved in 5% glucose (group I) or in 20% Intralipid at a final concentration of 1.5 (group II) or 3 mg mL-1 (group III). AMB was measured by liquid chromatography in plasma and in trypsin-dissolved fibrin clots up to 72 h after the infusion. No significant differences in AMB plasma and interstitial-fluid concentration kinetics between the three modes of administration were found. AMB penetration into fibrin clots was slow, with no significant differences between treatments. Thus, formulation of AMB in Intralipid does not modify either the drug's interstitial or plasma kinetics at equivalent doses.