Intravenous Administration Of Dexamethasone Research Articles

Pathogenesis of equine herpesvirus-1 in specific pathogen-free foals: primary and secondary infections and reactivation.

Six specific pathogen-free foals shown to be free of equine herpesvirus-1 and 4 (EHV-1 and -4) and lacking in maternally-derived antibodies were used to investigate the pathogenesis of EHV-1 in horses. Following primary intranasal inoculation with EHV-1 all foals showed signs of a mild, self-limiting upper respiratory tract infection. A leucopenia was observed, comprising both a lymphopenia and neutropenia. Virus was isolated from nasal mucus and buffy coat cells over several days during the clinical episode and after the animals became clinically normal. Notwithstanding the mildness of the clinical disease, virus was not eliminated completely and intravenous administration of dexamethasone resulted in reactivation of latent EHV-1 in animals which had received only a single dose of the virus. In a second infection given to four foals, 61 days after the primary inoculation, no clinical signs were observed, haematological changes were minimal and viraemia was absent.

Effects of intravenous and oral dexamethasone on selected lymphocyte subpopulations in normal subjects

Our studies describe the effects of 1 mg oral (PO) and intravenous (IV) administration of dexamethasone (DEX) on certain subpopulations of circulating lymphocytes in normal subjects. We compared the outcomes of PO and IV DEX administration because of individual differences in gastro-intestinal absorption of DEX and the issue of noncompliance in patients undergoing the dexamethasone suppression test (DST). Both routes of DEX administration were equally effective in suppressing plasma cortisol levels below 5 μg/dl, the customary criterion level. Both routes of DEX administration also significantly decreased the percent and absolute number of CD4+ cells, the CD4+/CD8+ ratio, and the percent and absolute number of virgin, but not of memory, CD4+ cells.

Pharmacokinetics and antibacterial efficacy of cefpirome (HR 810) in experimental Escherichia coli and Haemophilus influenzae type b meningitis

Cefpirome (HR 810) is a new cephalosporin related to cefotaxime that has potent bactericidal activity against a broad spectrum of gram-negative and gram-positive organisms. The pharmacokinetics and bacteriological efficacy of cefpirome administered as a single intravenous dose were assessed in rabbits with experimental Haemophilus influenzae type b and Escherichia coli K1 meningitis. The mean penetrations into the cerebrospinal fluid (CSF) in relation to the amount of drug in serum of animals infected with H. influenzae and E. coli were 25 and 54%, respectively. The median CSF bactericidal titers were 1:128 against both organisms at 1 h of uninfected animals, the mean penetration was 4.5%. There was a significant reduction in the concentrations of bacteria in CSFs of both groups of animals treated with cefpirome compared with that in untreated groups. Mortality was also significantly lower in treated animals than it was in untreated animals. Intravenous administration of dexamethasone before the cefpirome dose did not compromise penetration, bactericidal titers, or antibacterial activity of cefpirome in CSF.

The use of 2-hydroxypropyl-β-cyclodextrin as a vehicle for intravenous administration of dexamethasone in dogs

Dexamethasone (Dex) was administered to 6 mongrel dogs in a dose of 5 mg/kg as the sodium salt of its phosphate ester or as an inclusion complex in 2-hydroxypropyl-β-cyclodextrin (HPCD). Blood and urine were collected and analyzed for dexamethasone by HPLC. The area under the plasma concentration time curve (AUC) of dexamethasone during the first hour was significantly greater after the administration of the Dex-HPCD complex compared to the phosphate ester prodrug (1.63 ± 0.13 vs 1.04 ± 0.10 μg h ml −1). In addition, the renal clearance (CL ren) was significantly higher after administration of the HPCD form (0.91 ± 0.20 vs 0.52 ± 0.20 ml min −1 kg −1). There was no difference between treatments for other pharmacokinetic parameters of dexamethasone. Hence, intravenous injection of dexamethasone in HPCD allows direct administration of this poorly soluble steroid without any prodrug conversion. The higher plasma levels during the first hour after administration may be advantageous for the treament of emergency situations.

Adrenal function testing in the cat: the effect of low dose intravenous dexamethasone administration

The plasma cortisol responses of 11 normal cats to intravenous dexamethasone at a dose rate of 0.01 mg kg-1 whole bodyweight, were evaluated. Mean plasma cortisol concentrations decreased significantly (P less than 0.01) at three hours and eight hours following dexamethasone administration. Results of this study indicate that plasma cortisol levels are significantly decreased for at least eight hours following low dose intravenous dexamethasone administration in normal cats.

An uncommon adverse effect following bolus administration of intravenous dexamethasone

An uncommon adverse effect following bolus administration of intravenous dexamethasone

Phenytoin impairs the bioavailability of dexamethasone in neurological and neurosurgical patients.

Plasma concentration-time data after oral and intravenous administration of dexamethasone have been subjected to pharmacokinetic analysis in six neurological or neurosurgical patients taking the steroid with phenytoin, and in nine patients (one studied twice) taking dexamethasone without phenytoin. An additional patient was studied before and during phenytoin intake. Apparent volume of distribution was similar in the two groups, but the group treated with phenytoin had an almost statistically significantly shorter dexamethasone mean terminal half-life, an approximately trebled mean plasma clearance, and a mean oral bioavailability of the steroid of only 33%, compared with a mean 84% oral bioavailability in those not receiving phenytoin. To achieve a given plasma dexamethasone concentration, patients treated with the steroid and phenytoin may need oral dexamethasone doses several times those required by patients not receiving phenytoin.

Lack of rapid effects of cortisol on parathyroid hormone levels in cattle.

Experiments were performed to study plasma concentrations of parathyroid hormone in association with short-term changes of cortisol and dexamethasone. Parathyroid hormone was not significantly modified during 3-hour intravenous infusions of cortisol, leading to marked elevations (p less than 0.001) of plasma cortisol levels, and during intravenous administration of dexamethasone. Thus glucocorticoids, at least in cattle, apparently cause no short-term changes of plasma parathyroid hormone levels.

The effect of aerosol ipratropium bromide and salbutamol on exercise tolerance in chronic bronchitis.

In a double-blind placebo controlled trial in 24 patients fulfilling the MRC criteria for chronic bronchitis, ipratropium bromide 40 microgram and salbutamol 200 microgram produced similar and significant (P less than 0.001) increases in forced expiratory volume in one second (FEV1) and forced vital capacity (FVC). A greater increase in FEV1 and FVC was seen when both drugs were used together, but this increase did not differ significantly from that produced by either drug alone. Salbutamol increased 12-minute walking distance significantly (P less than 0.001) by 62 +/- 15 metres, whereas the increase of 43 +/- 15 metres observed after ipratropium was not significant (P less than 0.05). With both drugs in combination 12-minute walking distance increased by 72 +/- 15 metres, but this change was not significantly different from that observed with salbutamol alone. If aerosol bronchodilators in the doses used in this study are to be given with a view to improving exercise tolerance in such patients than salbutamol would appear to be the aerosol of choice.

The effect of large doses of dexamethasone on the cerebrospinal fluid pressure in patients with supratentorial tumors.

The effect of large doses of dexamethasone (80 mg) on the cerebrospinal fluid pressure (CSFP) was investigated with continuous lumbar CSFP measurement over 24 h in 10 patients with supratentorial cerebral tumors and clinical signs of elevated intracranial pressure. There was a further slight rise in CSFP with an unchanged pressure pattern in the course of observation of the untreated control group. A marked lowering of CSFP was observed within 6 h after initial intravenous administration of dexamethasone to seven of the treated patients. In four of the treated patients an unequivocal and in five only a moderate CSFP lowering was measured at the end of the registration. One patient had a slight rise in pressure. The plateau waves of all the patients treated decreased in height, frequency and duration within the first hours, while fluctuations in pressure level and CSFP amplitude were reduced.

Development of Neutrophilia by serially increasing doses of dexamethasone.

Dexamethasone (4-8 mg/m2 body surface area) was given orally or intravenously to six normal volunteers. The maximum neutrophil count occurred 4-6 h after oral or intravenous administration of dexamethasone and was due almost entirely to an increase in mature neutrophils; concomitantly there was a lymphocytopenia. A second rise in the neutrophil count occurred 24 h after oral ingestion of dexamethasone, coinciding with a lymphocytosis. Neutrophil alkaline phosphatase (NAP) activity during development fell as the neutrophil count rose. Other haematological values were unchanged except for small increments in erythrocyte sedimentation rate (ESR). Sodium concentration in serum and urine remained normal but urinary potassium excretion and urine volume increased after the intravenous dose. There was a direct relationship between plasma concentration of dexamethasone and the rise in neutrophil count following intravenous but not oral administration. The concentration of dexamethasone in plasma fell to half its peak value in 2-6 h. Dexamethasone-induced neutrophilia was similar to that induced by other corticosteroids. Dexamethasone in a dose of 6 mg/m2 produced minimal discomfort while inducing an adequate neutrophilia in the volunteers.

Factors Affecting the Efficiency of Filtration Leukapheresis

Continuous flow filtration leukopheresis was performed on normal volunteer donors with and without intravenous administration of dexamethasone. Although granulocyte counts were increased in steroid treated donors and almost 20% more cells were presented to the filters, the final yield of granulocytes was slightly decreased and the efficiency of collection during a two- to three-hour leukapheresis was statistically significantly decreased.

Effects of urethane on pituitary-adrenal function in the rat.

SummaryUrethane anesthesia produces elevated plasma concentrations of corticosterone (B) that are sustained over a 4-hour observation period. The elevated B levels are reduced after intravenous administration of dexamethasone (20 μg/100 ml body weight) within 3–4 hr, although the steroid suppression of ACTH release was not complete. Histamine (2000 mg), insulin (0.4 U), formalin (1 ml of 10% solution) and vasopressin (100 mU) each elicited an increase in plasma corticosterone levels in dexamethasone-pre-treated rats. No increments were observed after administration of the same agents in hypophysectomized rats.The assistance of Mrs. N. L. Swygert and Miss Katherine Egan is gratefully acknowledged.