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PubMed1984

Effect of cell cycle position on dexamethasone binding by mouse and human lymphoid cell lines: correlation between an increase in dexamethasone binding during S phase and dexamethasone sensitivity.

We determined the effect of cell cycle position on the amount of dexamethasone that was specifically bound by mouse and human lymphoid cell lines. Cell lines that were either sensitive or resistant to growth inhibition by dexamethasone were compared. Exponentially growing cells were separated by centrifugal elutriation into fractions that corresponded to different positions in the cell cycle. The cell cycle phase distribution of each fraction was estimated by flow cytometry and autoradiography. The amount of dexamethasone bound per cell in each fraction was measured by a whole cell binding assay. In three dexamethasone-sensitive cell lines (two mouse and one human), we found that the amount of dexamethasone bound per cell increased 2-4-fold between G1 phase and S phase, and then decreased during G2/M phase. Results were the same when the amount of dexamethasone bound per milligram of cell protein was measured. Binding affinity was the same during G1 phase and S phase, but the proportion of bound dexamethasone that translocated to the nucleus was greater during S phase. In contrast, we found that the amount of dexamethasone bound per cell by three dexamethasone-resistant cell lines (two mouse and one human) did not increase during S phase. Our results indicate that cell cycle changes in dexamethasone binding are not simply related to changes in cell protein or cell volume during the cell cycle. An increase in dexamethasone binding during S phase may be required for dexamethasone to inhibit cell growth, and a failure of dexamethasone binding to increase during S phase might represent a new mechanism of dexamethasone resistance in lymphoid cells.

Animals↗
PubMed2000

Dexamethasone metabolism in dexamethasone suppression test suppressors and nonsuppressors.

BACKGROUND: Variable dexamethasone kinetics is a possible confound in the dexamethasone suppression test. Modifications to include dexamethasone plasma levels and specific dexamethasone "windows" have been proposed. Our study aims to validate our proposed dexamethasone windows in an independent sample of 121 subjects. METHODS: We performed dexamethasone suppression tests in 162 subjects with mixed psychiatric diagnoses. Dexamethasone levels and beta-phase half-life of dexamethasone were computed for suppressors and nonsuppressors. RESULTS: Dexamethasone levels were lower in nonsuppressors than in suppressors. Dexamethasone levels correlated inversely with cortisol levels in the total sample, but were nonsignificant or weakly associated in those samples restricted to the windows. The beta-phase half-life of dexamethasone was shorter in nonsuppressors. The dexamethasone windows were validated at 3:00 PM and 10:00 PM. We propose 4.0 ng/mL as a revised upper limit of the 8:00 AM dexamethasone window. CONCLUSIONS: The plasma dexamethasone level is confirmed as a confound in the dexamethasone suppression test through more rapid dexamethasone clearance in nonsuppressors. Application of dexamethasone windows will reduce this source of test variance.

Adrenal Cortex Function Tests↗
PubMed1986

Dexamethasone suppression testing in chronic renal failure: pharmacokinetics of dexamethasone and demonstration of a normal hypothalamic-pituitary-adrenal axis.

The status of the hypothalamic-pituitary-adrenal axis in chronic renal failure (CRF) was examined by dexamethasone suppression testing (DST) using oral overnight, oral and iv 8-h daytime, and standard 48-h oral dosage protocols. Based on data obtained after iv administration of dexamethasone, the daytime study was used to calculate pharmacokinetic parameters for dexamethasone (clearance, volume of distribution at steady state, and terminal t1/2). None of a group of seven uremic patients had suppressed plasma cortisol concentrations after administration of 1 mg dexamethasone, orally, the night before. Six normal subjects and six patients with CRF participated in the pharmacokinetic study. There was no significant difference between the groups with respect to clearance, volume of distribution at steady state, or t1/2 of dexamethasone, indicating that patients with CRF metabolize dexamethasone in a fashion similar to that of normal subjects. Daily patterns of plasma cortisol determined between 0800-1600 h on a day when dexamethasone was not administered were similar in normal subjects and CRF patients. However, the degree of suppression of plasma cortisol after dexamethasone was significantly greater in the normal subjects (P less than 0.01), possibly due to a prolonged cortisol t1/2 in CRF. Nevertheless, the CRF patients did have decreased plasma cortisol levels from 4-8 h after iv and from 4-7 h after oral dexamethasone. The bioavailability of dexamethasone was not significantly different between the groups. When 48-h oral DSTs were performed in the CRF group, four of five patients had normal responses. The one patient who did not suppress had low levels of plasma dexamethasone, presumably due to decreased gastrointestinal absorption of dexamethasone. These results indicate that the metabolism of dexamethasone is similar in CRF patients and normal subjects, that normal suppression of plasma cortisol can be achieved in uremia if the duration of dexamethasone administration is prolonged sufficiently to compensate for the prolongation of cortisol t1/2 in CRF, and that it is essential to measure plasma dexamethasone as well as cortisol levels to interpret the results of a DST in CRF patients.

Administration, Oral↗
PubMed2002

Cortisol and ACTH response to oral dexamethasone in obesity and effects of sex, body fat distribution, and dexamethasone concentrations: a dose-response study.

There is increasing evidence that the abdominal obesity phenotype may be associated with multiple alterations of the hypothalamic-pituitary-adrenocortical (HPA) axis activity in both sexes. Our hypothesis is that the lack of adequate cortisol suppression after the dexamethasone test may constitute an indirect marker of HPA axis hyperactivity in the presence of the abdominal obesity phenotype. A total of 34 normal-weight (13 men and 21 women) and 87 obese (36 men and 51 women), healthy, nondepressed subjects therefore underwent four different dexamethasone suppression tests randomly performed at varying intervals of at least 1 wk between each test. After a standard overnight 1-mg dexamethasone test, which served as a reference, three other tests were randomly performed at 1-wk intervals by administering 0.0035, 0.0070, and 0.015 mg oral dexamethasone per kilogram of body weight overnight. Blood samples were obtained for cortisol, ACTH, and dexamethasone. Results were analyzed separately in men and women as well as in normal-weight [body mass index (BMI) < or = 25 kg/m(2)] and overweight or obese (BMI > 25 kg/m(2)) subjects. The waist circumference and the waist to hip ratio (WHR) were used as markers of body fat distribution. After the standard 1-mg test, cortisol suppression was greater than 90% in all subjects. However, after each test, obese women had significantly higher values of percent cortisol and percent ACTH suppression than normal-weight women without any difference between obese and normal-weight men. Considering the response to the three variable-dose tests, a clear dose- response pattern (P < 0.001 for trend analysis) in percent cortisol and percent ACTH suppression was found in all subjects. After each test men had significantly higher dexamethasone levels than women, regardless of BMI. However, obese women, but not men, had significantly higher dexamethasone levels after each test than their normal-weight counterpart. Plasma dexamethasone concentrations were dose related (P < 0.001 for trend analysis) in all subjects, but the dose-related increase was significantly higher in normal-weight men than normal-weight women, whereas it was similar in obese subjects of both sexes. Stepwise multiple regression analysis revealed that both percent cortisol and percent ACTH variations were significantly and negatively influenced by dexamethasone levels, as well as by waist circumference values in men, and independently by BMI and waist circumference in women. However, in contrast to what has been found in men, a divergent contribution of BMI and waist circumference was found in women indicating that, with increasing waist values, a smaller suppression of the HPA axis was found with respect to that expected on the basis of BMI values. In conclusion, this study provides data of both physiological and physiopathological relevance. Overall, our data indicated that adjustment of the dexamethasone dose to body weight does not seem to substantially improve the sensitivity of the test, even in obese individuals, particularly when near-maximal doses are administered. However, this study demonstrated a highly significant effect of dexamethasone blood level concentrations on cortisol and ACTH suppression to low-dose dexamethasone tests. In addition, a significant effect of gender on postdexamethasone cortisol concentrations, suppression of the HPA axis, and dexamethasone levels were found, which may be dependent on related differences in both cortisol and dexamethasone metabolism. We showed that pituitary sensitivity to feedback inhibition by dexamethasone is preserved in obesity in both sexes even at low dosages. On the other hand, our data suggest that, at least in women, abdominal fat distribution may partially counteract the progressively greater suppressibility of the HPA axis that would be expected according to increasing BMI.

Adipose Tissue↗
PubMed1981

Dexamethasone concentrations in plasma and milk of cows following the injection of long- and short-acting dexamethasone esters.

A radioimmunoassay has been developed for the measurement of dexamethasone in plasma and milk of cows injected with long- and short-acting dexamethasone esters. Dexamethasone antiserum was produced by injecting cows with a dexamethasone-21-hemisuccinate-human serum albumin complex. The antisera was highly specific for dexamethasone, cross-reacting less than 0.7% for all endogenous steroids tested. Plasma concentrations of dexamethasone in cows injected intramuscularly with either 20 mg dexamethasone-21 trimethyl acetate (n = 2) or the tributyl derivative (n = 2) reached a peak level of 0.6-1.1 ng/ml in 2-6 days then declined to undetectable levels (less than 0.15 ng/ml) and 14 days after injection. In general, dexamethasone concentrations in milk were 0.3-0.5 times the plasma concentrations but showed the same pattern of values. Plasma dexamethasone concentrations were also determined in three lactating dairy cows injected intramuscularly with tritiated dexamethasone-21 trimethyl acetate. In these cows plasma dexamethasone concentrations, as determined by isotopic dilution, reached maximal levels of 1.1-1.6 ng/ml in 1-3 days then declined to levels of around 0.05 ng/ml within 30 days. The concentrations of dexamethasone in milk of two of these cows were, in general, similar to those found in plasma. In three cows injected intramuscularly with 20 mg dexamethasone sodium phosphate the concentrations of dexamethasone in plasma rose sharply to maximum levels of 24-70 ng/ml within 2-20 min after injection and fell to undetectable levels (less than 0.15 ng/ml) after 72 hr.

Animals↗
PubMed1982

Dexamethasone suppression tests: usefulness of simultaneous measurement of plasma cortisol and dexamethasone.

The effect of oral dexamethasone on the plasma content of cortisol and dexamethasone was investigated in 175 patients suspected of having Cushing's syndrome. Plasma concentrations of cortisol and dexamethasone were measured by specific radioimmunoassays at 08.00 h following administration of either a low-low (0.5 mg), low (1.0 mg), high (4.0 mg) or high-high (8.0 or more mg) dose of dexamethasone at midnight. All seventeen patients with documented Cushing's syndrome exhibited resistance to the action of low-low and/or low dose dexamethasone on suppression of 08.00 h plasma cortisol content. Nine of twelve patients with pituitary dependent Cushing's syndrome had plasma cortisol values of less than 166 nmol/l following high-high dose testing. In 157 patients with suspected Cushing's syndrome, standard dexamethasone testing was considered unsatisfactory in at least 20%. After low-low or low dose tests 11% had supranormal cortisol values, but plasma cortisol content overlapped with values observed in patients with Cushing's syndrome only when plasma dexamethasone content was less than 5.6 nmol/l. Twelve per cent of patients suspected of having Cushing's syndrome had sufficient elevation of plasma dexamethasone values after low dose testing so that marked reduction of plasma cortisol might be expected even in patients with pituitary dependent Cushing's syndrome. Four patients receiving anticonvulsants had subnormal plasma levels of dexamethasone for the dose administered, but all exhibited normal suppression when plasma levels of dexamethasone and cortisol were correlated simultaneously. In summary, there is considerable variation in the plasma content of dexamethasone following oral doses. Simultaneous measurement of both plasma levels of dexamethasone and cortisol has proved most useful in identifying patients with unsatisfactory dexamethasone suppression tests.

Adolescent↗
PubMed1987

Escape from dexamethasone-induced ACTH and cortisol suppression by corticotrophin-releasing hormone: modulatory effect of basal dexamethasone levels.

The response of ACTH and cortisol to corticotrophin-releasing hormone (CRH) after pretreatment with various doses of dexamethasone was investigated in five healthy subjects. The five subjects participated in six experiments. In each experiment 200 micrograms ovine CRH was administered as an i.v. bolus injection at 0900 h after pretreatment with respectively: (A) 1 mg dexamethasone orally at 2300 h in the evening before CRH injection, (B) 2 mg dexamethasone orally at 2300 h in the evening before CRH injection, (C) 4 mg dexamethasone orally at 2300 h in the evening before CRH injection, (D) 2 mg dexamethasone orally at 2300 h in the evening before CRH injection, followed by 2 mg dexamethasone orally 1 h before CRH, (E) no dexamethasone and (F) 1 mg dexamethasone orally 1 h before CRH injection. In spite of overnight suppression with a single dose of dexamethasone CRH elicited cortisol rises in all individuals (experiments A-C). Dexamethasone pretreatment in experiment D abolished the CRH-induced stimulation of the pituitary-adrenal axis. There was a significant and negative correlation between the basal dexamethasone levels (i.e. the dexamethasone levels immediately before CRH administration) in the experiments A-D and the areas under the individual ACTH (R = -0.62; P less than 0.01 by Spearman's rank correlation test) and cortisol (R = -0.81; P less than 0.001 by Spearman's test) curves, i.e. the lower the basal dexamethasone levels, the greater the rise in ACTH and cortisol levels after CRH administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗
PubMed1999

Systemic dexamethasone concentration in horses after continued topical treatment with an ophthalmic preparation of dexamethasone.

OBJECTIVE: To determine concentrations of dexamethasone in serum and urine of horses treated repeatedly with a topically administered ophthalmic dexamethasone preparation. ANIMALS: 4 clinically normal horses (2 mares, 2 geldings). PROCEDURE: 0.1% dexamethasone ophthalmic ointment was administered to the left eye of each horse every 5 to 9 hours for 8 consecutive days, yielding an estimated cumulative dexamethasone dose of 6.4 microg/kg of body weight. Serum and urine samples were obtained before the first dexamethasone treatment, on days 4 and 8 of treatment, and 24, 48, and 96 hours after cessation of treatment. To detect small concentrations of dexamethasone, serum and urine samples were analyzed by use of a competitive enzyme immunoassay. RESULTS: During the period of continued topical treatment, serum dexamethasone concentrations increased to between 0.10 and 0.49 ng/ml, then decreased below the limit of detection (0.06 ng/ml) within 24 hours after cessation of treatment. Dexamethasone also was detected in urine samples at concentrations of up to 0.98 ng/ml. CONCLUSIONS: Repeated topical administration of dexamethasone ophthalmic ointment generated low, but detectable glucocorticoid concentrations in serum and urine. CLINICAL RELEVANCE: Because treatment of performance horses with dexamethasone is prohibited for most types of competitions and because enhanced glucocorticoid detection methods may result in positive test results, owners and trainers may wish to reconsider entering horses in competitions during periods of treatment with ophthalmic dexamethasone preparations.

Administration, Topical↗
PubMed1992

Adrenal steroid receptor activation in rat brain and pituitary following dexamethasone: implications for the dexamethasone suppression test.

The dexamethasone suppression test (DST) has been used extensively to evaluate feedback inhibition of the hypothalamic-pituitary-adrenal (HPA) axis by adrenal steroids. Nevertheless, it remains unclear at what level of the HPA axis and through which adrenal steroid receptor subtype dexamethasone exerts its inhibitory effect. Because adrenal steroid receptor activation is an important prerequisite for dexamethasone to affect cellular function, HPA axis tissues that exhibit evidence of receptor activation following dexamethasone administration are likely site(s) of action for this synthetic hormone to inhibit HPA axis activity. Therefore, type-I and type-II adrenal steroid receptor activation was assessed in the pituitary, hypothalamus, and hippocampus of intact and adrenalectomized rats after overnight exposure to various oral doses of dexamethasone. Results with dexamethasone were compared to similar studies using corticosterone, the endogenous glucocorticoid of the rat. All dexamethasone doses led to significant type-II receptor activation in the pituitary, whereas only an exceedingly high dexamethasone dose activated type-II receptors in the hippocampus and hypothalamus. Dexamethasone had little effect on type I receptors in any tissue at any dose. In contrast, corticosterone significantly activated type-I receptors in all tissues, whereas it activated type-II receptors in the brain and not the pituitary at physiological concentrations. Because dexamethasone activated pituitary type-II receptors at blood concentrations that did not activate type-II receptors in the brain, these results suggest that the DST in humans may primarily be a measure of type-II adrenal steroid receptor feedback inhibition at the level of the pituitary.

Adrenalectomy↗
PubMed1988

Inhibition of prostaglandin synthesis in brain of rat by dexamethasone: lack of effect of dexamethasone phosphate ester and various hormonal steroids.

The present study was designed in order to characterize the inhibitory effect of dexamethasone upon the synthesis of prostaglandins (PG) in the brain of the rat. Rats were treated with dexamethasone (20 mg/kg b.w.) and sacrificed 0-76 hr after administration of the drug. The rate of synthesis and release of PGE2 was followed by 1 hr of incubation of slices of cortex taken from these rats, in Krebs-Ringer solution. A significant inhibition occurred at 8 hr and maximal inhibition (45%) was attained at 16 hr after injection. A gradual increase in the rate of synthesis up to control values occurred between 24 and 76 hr. A dose-response study, at the range of 2-40 mg/kg, showed that a significant decrease was noted at 6 mg/kg and it was maximal (45% inhibition) at 20 and 40 mg/kg. Administration of dexamethasone-sodium-phosphate, as well as other synthetic glucocorticoids and various steroidal hormones (20 microM), failed to inhibit the biosynthesis of prostaglandins under the same experimental conditions. The effect of dexamethasone and dexamethasone phosphate on synthesis of PGE2 was also studied under in vitro conditions at 5 and 20 microM. When slices of cortex from intact rats were incubated for 1 or 2 hr in the presence of either dexamethasone or dexamethasone phosphate only dexamethasone was effective in inhibiting the synthesis of PGE2. The present results demonstrate that the inhibition of the synthesis of prostaglandins in brain by dexamethasone is both time- and dose-dependent. The lack of effect of closely related glucocorticoids demonstrate that the effect is highly specific to dexamethasone.

Animals↗
PubMed2002

Dose response of dexamethasone for the enhanced ocular hypotensive response to epinephrine in rabbits with prior dexamethasone treatment.

We have previously shown that administration of epinephrine to the rabbit eye with dexamethasone pretreatment resulted in a significant decrease in intraocular pressure (IOP), compared to the use of epinephrine alone. Furthermore, this decrease in IOP is dose-dependent on epinephrine with the largest response of decrease of IOP occurring at the lower doses of epinephrine. We now extend this study to determine whether the decrease in IOP is dose-dependent on dexamethasone. Rabbit eyes were pretreated with five applications of topical dexamethasone or saline, administered at fifteen-minute intervals. Eyes were then treated with 0.005% epinephrine (0.01% epinephrine bitartrate). IOP was monitored for the next four hours. Different groups of rabbits received varying concentrations of dexamethasone base, from 0.0004% to 0.07% (dexamethasone phosphate), and a dose response curve was obtained. When compared to eyes treated with epinephrine alone, eyes pretreated with dexamethasone showed a significantly greater decrease in pressure at free base dexamethasone concentrations of 0.07%, 0.007% and 0.0007%, with the greatest difference at the 0.007% concentration (mean = 6.8 mm Hg). Similarly, the duration taken for the IOP to return to baseline levels was prolonged in the groups receiving dexamethasone pretreatment. The synergism between dexamethasone and epinephrine in lowering IOP may be a useful alternative in the treatment of ocular hypertension and glaucoma especially using a combination of a low dose of epinephrine with a low dose of dexamethasone.

Animals↗
PubMed1983

Stability of sterile dexamethasone acetate suspensions and dexamethasone sodium phosphate injections submitted by U.S. hospitals.

The stability of sterile dexamethasone acetate suspensions and dexamethasone sodium phosphate injections that had been stored in hospital pharmacies across the United States was studied. Through a voluntary FDA drug stability program, all hospital pharmacies in the United States were asked in October 1981 to complete a response card indicating information about the sterile dexamethasone acetate suspensions and dexamethasone sodium phosphate injections they had in stock. Based on the responses, FDA selected 21 samples of sterile dexamethasone acetate suspensions (representing two manufacturers) and 114 samples of dexamethasone sodium phosphate injection (representing 11 manufacturers). These samples were analyzed for identification, pH, and strength. All samples of sterile dexamethasone acetate suspension met USP requirements. Eleven samples of dexamethasone sodium phosphate injection representing 10 lots from three manufacturers failed USP assay requirements for strength. All samples that failed to meet strength requirements showed evidence of degradation by oxidation. Sterile dexamethasone acetate suspensions appear to be stable when stored under actual marketplace conditions, but there is a problem with the shelf-life stability of dexamethasone sodium phosphate injections made by some manufacturers.

Dexamethasone↗
PubMed1984

Mechanisms of anti-inflammatory action of dexamethasone: blockade by hydrocortisone mesylate and actinomycin D of the inhibitory effect of dexamethasone on leukocyte infiltration in inflammatory sites.

The present study was designed to clarify molecular mechanisms underlying inhibitory effect of dexamethasone on leukocyte infiltration in the inflammatory site. For the assay of leukocyte infiltration, two or four blebs were made s.c. on the back of rats by injecting with 2% carboxymethyl cellulose solution containing a chemoattractant, casein. Leukocyte accumulation in the bleb was inhibited considerably by local application of dexamethasone at a concentration of 0.6 X 10(-6) M. Hydrocortisone mesylate, which was reported in the study with hepatoma tissue culture cells to be a long-acting antagonist against glucocorticoid in binding to the corticoid receptor, blocked the above leukocyte inhibitory effect of dexamethasone when applied simultaneously with dexamethasone. The leukocyte infiltration was unaffected by the application of hydrocortisone mesylate alone. Treatment with androstenedione, which was reported to be inactive in the hepatoma tissue culture cells, did not interfere with the inhibitory effect of dexamethasone at all. Actinomycin D, when applied simultaneously with dexamethasone, significantly suppressed the leukocyte-inhibitory effect of dexamethasone. In contrast with those observations, the inhibitory effect of dexamethasone was not affected at all in cases that actinomycin D and hydrocortisone mesylate, respectively, were applied after the administration of dexamethasone. These results indicate essential roles of glucocorticoid receptor and gene expression for the manifestation of the inhibitory effect of dexamethasone on leukocyte infiltration in the inflammatory site.

Androstenedione↗
PubMed1993

Circulating concentration of dexamethasone in healthy dogs, dogs with hyperadrenocorticism, and dogs with nonadrenal illness during dexamethasone suppression testing.

Concentration of dexamethasone was determined in plasma or serum samples from dogs after i.v. administration of a low dose (0.01 mg/kg of body weight) or high dose (0.1 mg/kg) of dexamethasone. On the basis of history, clinical signs of disease, and degree of cortisol suppression in response to dexamethasone, dogs were assigned to these groups: healthy dogs, dogs with nonadrenal illness, and dogs with hyperadrenocorticism. Four hours after administration of the low dose of dexamethasone, concentration of the steroid was reduced (P < 0.05) in dogs with hyperadrenocorticism, compared with healthy dogs, but not compared with values from dogs with nonadrenal illness. By 8 hours after dexamethasone administration, values were similar across groups. Dexamethasone concentration 4 and 8 hours after high-dose administration was similar between healthy dogs and dogs with hyperadrenocorticism. Concentration of dexamethasone 4 and 8 hours after its administration overlapped after the 2 doses. For example, in 11 of 66 dogs from all groups, concentration measured 4 hours after the low dose was greater than the minimal concentration determined in the 18 dogs given the high dose. These data indicate that dexamethasone metabolism may be altered in dogs with hyperadrenocorticism, and that individuals may have appreciable variability in dexamethasone clearance. Such variability provides a possible explanation for false-positive and false-negative results associated with dexamethasone suppression testing in dogs.

Adrenocortical Hyperfunction↗
PubMed1987

Neuroendocrine aspects of primary endogenous depression. II. Serum dexamethasone concentrations and hypothalamic-pituitary-adrenal cortical activity as determinants of the dexamethasone suppression test response.

To determine the contribution of serum dexamethasone concentrations and hypothalamic-pituitary-adrenal cortical activity before dexamethasone administration to the dexamethasone suppression test (DST) response, a series of stepwise discriminant function analyses were performed for 40 patients with definite endogenous depression and 40 matched normal control subjects. The 24-hour serum cortisol concentration before dexamethasone administration and the serum dexamethasone concentrations at 8, 16, and 24 hours after administration served as the independent variables, and the DST "escaper"/"suppressor" dichotomy served as the dependent variable. While both types of independent variables significantly influenced the DST response, the major factor that contributed to the discrimination of escapers from suppressors was the 24-hour cortisol concentration before dexamethasone administration. Sixteen hours after dexamethasone administration, when the DST had the highest positive predictive value, serum dexamethasone concentrations significantly influenced DST outcome only when they were below a certain threshold level. At this time, hypothalamic-pituitary-adrenal cortical hyperactivity before dexamethasone administration accounted for approximately two thirds of the incidence of DST nonsuppression.

Circadian Rhythm↗
PubMed1991

Serial dexamethasone suppression tests and plasma dexamethasone levels. Effects of clinical response to electroconvulsive therapy in major depression.

Serial 1-mg dexamethasone suppression tests with concurrent plasma dexamethasone assessments were conducted in 58 patients with endogenous depression treated with electroconvulsive therapy (ECT). Plasma cortisol levels decreased significantly from pretreatment to immediately posttreatment, and they declined further during the first week after the ECT course, when patients remained drug free. Plasma dexamethasone levels showed an opposite pattern of progressive increases over these three time points. The progressive changes in plasma dexamethasone and cortisol levels seen during the week after ECT indicate that alterations in the bioavailability of dexamethasone and in hypothalamic-pituitary-adrenal axis function may be incomplete immediately after the ECT course. This may partly account for previous inconsistencies in serial dexamethasone suppression test findings with this treatment modality. The major finding was that clinical response was associated with increased plasma dexamethasone levels, whereas changes in cortisol levels were independent of clinical outcome. With ECT, changes in plasma dexamethasone levels may be more related to changes in clinical state than changes in postdexamethasone cortisol levels. The extent to which clinical recovery with other treatments in depression is associated with altered bioavailability of dexamethasone and perhaps other compounds is unknown and in need of investigation.

Age Factors↗
PubMed1998

Dexamethasone and dexamethasone phosphate detected by 1H and 19F NMR spectroscopy in the aqueous humour.

To apply nuclear magnetic resonance (NMR) spectroscopy to study the penetration of dexamethasone phosphate into the aqueous humour from rabbit following topical administration. After topical administration of 0.1%, 1.0% and 10% dexamethasone phosphate solutions, respectively, samples of aqueous humour were aspirated, freeze-dried, redissolved in deuterium oxide and analyzed by high resolution 1H and 19F NMR spectroscopy. In order to study the lipophilic and hydrophilic metabolites of the drug, samples obtained after application of 1% dexamethasone phosphate were extracted with methanol/chloroform, and then extracted with perchloric acid. In all samples obtained from eyes denuded of the corneal epithelium prior to administration of dexamethasone, signals corresponding to the chemical shifts of the drug were identified in 19F NMR spectra. In the experiments performed with 1% dexamethasone phosphate, both dexamethasone and dexamethasone phosphate were detected in the aqueous humour. Using 10% dexamethasone phosphate solutions, signals from the drug were detected in 1H NMR spectra simultaneously with signals from about twenty other substances present in the aqueous humour. NMR spectroscopy appears to be a valuable method for studying dexamethasone metabolism and penetration into ocular tissues. It provides simultaneous detection of both the drug metabolites and other substances in the sample and might offer a complementary approach to other analytical methods.

Administration, Topical↗
PubMed1987

The dexamethasone suppression test: importance of dexamethasone concentrations.

Plasma dexamethasone concentrations and cortisol response to dexamethasone were measured in 29 normal healthy volunteers, 23 depressed patients, and 10 patients with anorexia nervosa at 4:00 PM postdexamethasone. In each of the 3 groups, nonsuppressors had lower dexamethasone concentrations than suppressors. Of the subjects with plasma dexamethasone at or below 0.7 ng/ml, a significantly higher proportion (48%) were nonsuppressors compared to the proportion above 0.7 ng/ml (14%), all of whom were patients. Plasma dexamethasone concentrations in a subgroup of depressed nonsuppressors were high (mean 1.35 ng/ml), whereas the remainder were low (0.42 ng/ml) and were similar to the normal nonsuppressors (0.35 ng/ml), suggesting different mechanisms for nonsuppression in the subgroups. Plasma dexamethasone concentrations were similar in nonendogenous and endogenous depressives, in men and women, and in medicated and drug-free patients. None of the variables of age, weight, history of weight loss, Hamilton depression rating score, predexamethasone cortisol, or postdexamethasone cortisol were significantly correlated with plasma dexamethasone, except for body weight and a history of weight loss in the depressed group only. Mean plasma dexamethasone concentrations increased significantly from week 1 to week 2 in 7 depressed patients, whereas plasma cortisol decreased; however, the relationship between dexamethasone and cortisol varied considerably for individual patients.

Adolescent↗