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PubMed1992

Kinetic-dynamic modeling of lymphocytopenia induced by the combined action of dexamethasone and hydrocortisone in humans, after inhalation and intravenous administration of dexamethasone.

Ten healthy male volunteers received 5 mg of dexamethasone sodium phosphate (DEX) i.v. and, on an other occasion, by way of nebulization. Plasma DEX and hydrocortisone (HC) concentrations as well as blood lymphocyte count (BLC) were monitored over 12 hr and at 24 to 28 hr after DEX administration. Bioavailability of DEX after inhalation was about 27% of DEX i.v. DEX-induced depletion of plasma HC could be predicted with a pharmacokinetic model. The reonset rate of HC-production was dependent of DEX dose. BLCs declined after DEX administration, reaching a minimum between 4- and 8-hr postdosing. The DEX- and HC-induced depression of BLC could be described by an integrated pharmacokinetic-pharmacodynamic competitive-interaction model that assumes that both agonists act on the same receptor. With this model the potency and efficacy of DEX and HC with respect to lymphocytopenia could be estimated simultaneously. The potency of DEX was 10 times greater than the potency of HC. The estimated efficacy suggests that HC is only a partial agonist; the maximal lymphocytopenic effect (Emax) of HC was estimated at 80% (27-99%) of the efficacy of DEX. Our results indicate that DEX should be preferred instead of HC in conditions in which the lymphocytopenic effect is the primary systemic corticosteroid treatment goal.

Administration, Inhalation↗
PubMed2004

The selective pulmonary vasodilatory effect of inhaled DETA/NO, a novel nitric oxide donor, in ARDS-a pilot human trial.

OBJECTIVES: To examine the effects of inhaled NONOates in patients with acute respiratory distress syndrome (ARDS). DESIGN: Case-series, phase I clinical trial. SETTING: A multidisciplinary intensive care unit in a tertiary teaching hospital. PATIENTS: Five consecutive patients with ARDS (men; age range, 47-76 years). MEASUREMENTS: DETA/NO (150 micromol) was aerosolized into the lungs of patients on mechanical ventilation via the endotracheal tube over 20 minutes. Hemodynamic parameters were measured and blood samples were taken before, during, and after inhalation. RESULTS: Compared to baseline values, pulmonary vascular resistance decreased until the end of the study period (180 minutes) while intrapulmonary shunting decreased significantly up to 45 min after DETA/NO aerosol administration. Inhaled DETA/NO had no effect on the systemic circulation (systemic blood pressure or cardiac output). CONCLUSIONS: Inhaled DETA/NO is a selective pulmonary vasodilator in patients with ARDS. However, a larger number of patients is required to confirm the findings of this pilot study.

Administration, Inhalation↗
PubMed1987

Urinary excretion of mercapturic acids and thiocyanate in rats exposed to acrylonitrile: influence of dose and route of administration.

Adult male Sprague-Dawley rats were exposed acutely to acrylonitrile (ACN) according to 1 of 3 different routes of administration: inhalation (6 h), i.v., or i.p. Urinary metabolites measured 24 h after administration were 2-cyanoethylmercapturic acid (CMA), 2-hydroxyethylmercapturic acid (HMA) and thiocyanate (TCN). In all 3 series of experiments, the relationship between excretion of total urinary metabolites and the degree of exposure was reasonably linear. However, there was a marked influence of the route of administration on the pattern of metabolic excretion. For example, after i.p. and i.v. injection CMA was the most important metabolite while after inhalation it was TCN. Our results also indicate an important effect of the dose on the pattern of excretion for all types of administration.

Acetylcysteine↗
PubMedDate not supplied

Inhaled nitric oxide improves pulmonary functions following massive pulmonary embolism: a report of four patients and review of the literature.

Acute pulmonary embolism increases pulmonary vascular resistance and may lead to acute right ventricular failure and cardiocirculatory collapse and respiratory failure, possibly resulting in substantial morbidity and mortality. Inhaled nitric oxide (NO) dilates pulmonary blood vessels and has been used to reduce pulmonary vascular resistance in patients with chronic thromboembolic pulmonary hypertension and acute respiratory distress syndrome. This case series describes our experience with inhaled NO administered to four patients suffering from acute massive pulmonary embolism following abdominal surgery. The four described patients recovering from small bowel resection, pancreatoduodenectomy, hemipelvectomy, or recent gastrointestinal bleeding had severe respiratory and hemodynamic deterioration due to pulmonary embolism. Each received inhaled NO (20-25 ppm) via the inspiratory side of the breathing circuit of the ventilator. Pulmonary and systemic blood pressures, heart rate, and lung gas exchange improved in all the patients within minutes after the initiation of NO administration. Inhaled NO may be useful in treating acute massive pulmonary embolism. This potential application warrants further investigation.

Acute Disease↗
PubMed2001

Inhaled nitric oxide administration during one-lung ventilation in patients undergoing thoracic surgery.

OBJECTIVE: To evaluate the effects of inhaled nitric oxide (iNO) on hemodynamics and oxygenation during one-lung ventilation (OLV) in the lateral decubitus position in patients undergoing elective thoracic surgery. DESIGN: Prospective study. SETTING: University hospital. PARTICIPANTS: Thirty consecutive patients scheduled for thoracotomy. INTERVENTIONS: Anesthesia consisted of thoracic epidural analgesia combined with general anesthesia (isoflurane, fentanyl, and vecuronium bromide). Systemic and pulmonary circulations were monitored with a radial artery catheter and a pulmonary artery catheter. Inhaled NO, 40 ppm, was administered during OLV, and the inhaled gas mixture was monitored for NO and nitrogen dioxide (NO2). Hemodynamic and oxygenation data were collected before and during inhaled NO administration. MEASUREMENTS AND MAIN RESULTS: Inhaled NO caused a reduction of pulmonary vascular resistance index from 249 +/- 97.6 dyne. sec. cm(-5) to 199.3 +/- 68.9 dyne. sec. cm(-5) (p < 0.05), without effects on systemic hemodynamics or impairment of oxygenation. A stratification of the patients according to values of QS/QT (< 30%, 30% to 44%, > or = 45%), PaO(2)/fraction of inspired oxygen (> or = 200, 100 to 199, < 100), and pulmonary hypertension (mean pulmonary arterial pressure < 24 or > or = 24 mmHg) showed that inhaled NO causes a significant reduction of mean pulmonary artery pressure in patients with pulmonary hypertension, mainly as a result of a reduction of pulmonary vascular resistance index, and improves oxygenation by reducing intrapulmonary shunt in patients with severe hypoxemia during OLV. CONCLUSIONS: Inhaled NO administration neither significantly decreased mean pulmonary arterial pressure in patients with normal pulmonary artery pressure nor improved oxygenation in nonhypoxic patients. Nevertheless, inhaled NO is effective in patients with pulmonary hypertension and hypoxemia during OLV.

Aged↗
PubMed2004

[Effectiveness and safety of fluticasone propionate in therapy of children suffering from asthma. Part II. Safety aspects of therapy with fluticasone propionate in asthmatic children].

Inhaled administration of glucocorticoid doesn't mean lack of systemic effects of drug. Bioavailability of steroid depends on oral absorption and absorption from respiratory system. In case of fluticasone propionate (FP) swallowed dose can be neglected because almost total (>99%) inactivation in liver during first pass. In second part of paper the most important safety parameters of therapy with FP are discussed, it means; influence on hypothalamic-pituitary-adrenal axis, growth and bone metabolism. Interpretation of potential side effects should differentiate between abnormal value of laboratory test and clinically important symptoms. Adrenal suppression depends on dose of FP and was found even after low dose (about 200 microg per day), but clinical value of this findings is unknown. Prolonged administration of high doses can suppress hypothalamic-pituitary-adrenal axis; exceptionally, it can induce adrenal insufficiency. Recommended doses of FP given 1 to 2 years doesn't cause growth retardation. Long term studies on influence of drug on final height are needed. FP as other inhaled corticosteroids, may transiently alter bone metabolism. Till now there are no evidences that this drug, when prescribed appropriately in standard doses for asthma control, may decrease the bone mineral density or induce osteoporosis and may increase the risk of bone fractures in asthmatic children. Effective asthma control achieved with FP therapy permits normal activity and development of asthmatic children which prevails over exceptionally noticed side effects.

Administration, Inhalation↗
PubMed1990

Short term inhalation of bromobenzene: methodology and absorption characteristics in mouse, rat and rabbit.

In a dynamic inhalation system, mice, rats and rabbits were exposed to bromobenzene vapour (250-3400 p.p.m.) for 4 hr. Blood concentrations of bromobenzene were determined by head-space gas chromatography. After inhalation of 1000 p.p.m. for 4 hr, concentrations of 153, 102 and 47 micrograms bromobenzene/ml blood were found in mice, rats and rabbits, respectively. In vitro experiments showed a blood/air partition coefficient at 37 degrees of approximately 200, which was reflected by a linear uptake of bromobenzene up to an air concentration of 2500 p.p.m. Compared with results obtained previously by intraperitoneal bromobenzene administration inhalation resulted in higher blood concentrations.

Absorption↗
PubMed2002

Amphotericin B disposition after aerosol inhalation in lung transplant recipients.

BACKGROUND: Bronchopulmonary fungal infections continue to be a major cause of morbidity and mortality in lung transplant recipients, and amphotericin B remains the drug of choice for prophylaxis of most fungal infections. Unfortunately, intravenous amphotericin B has numerous serious adverse effects; thus, nebulized amphotericin B could decrease the incidence of adverse effects seen with the intravenous formulation and provide high local concentrations in the lung tissue. We performed a prospective pilot study to characterize the bronchoalveolar lavage (BAL), lung tissue, and plasma concentrations of amphotericin B following inhalation administration to lung transplant recipients. METHODS: Amphotericin B 30 mg was administered by nebulizer prior to a routine bronchoscopy. Amphotericin B concentrations in BAL samples from the upper and lower lobes, transbronchial biopsies, and plasma (obtained by drawing a blood sample 30 min after the amphotericin B inhalation) were analyzed by HPLC. RESULTS: Eight patients were enrolled in the study (mean age 50.0 +/- 16.1 y; number of years posttransplant 3.0 +/- 1.9; type of transplant 5 double-lung, 3 single-lung). The mean amphotericin B concentration in the upper and lower lobe BAL samples were 0.68 +/- 0.36 and 0.50 +/- 0.31 microgram/mL, respectively. Amphotericin B concentrations, detected in only 2 of 5 biopsy samples, were 0.118 and 0.03 microgram/g. Amphotericin B was detected in the plasma of only 1 patient (0.19 mg/L). CONCLUSIONS: This pilot study demonstrated that detectable concentrations of amphotericin B can be attained in both the upper and lower BAL samples following aerosol administration. However, the frequency of the dose and duration of treatment still need to be determined in a larger study.

Administration, Inhalation↗
PubMed2003

Novel alternative methods for the delivery of drugs for the treatment of asthma.

Successful delivery of dry powder aerosols to the lung requires careful consideration of the powder production process, formulation and inhaler device. Newer production methods are emerging to prepare powders with desirable characteristics for inhalational administration. The conventional formulation approach of adding coarse lactose carriers to the drug to form binary powder systems to enhance powder flow and dispersion properties has been expanded to using finer carrier particles and hydrophobic materials, as well as ternary systems. Particle morphology and surface properties have also been explored to enhance powder performance. For the inhaler device, the new generation inhalers are designed to reduce or completely decouple the influence of air flow on the aerosol generation. Each of these determinants for powder aerosol delivery is reviewed with a strong focus on the patent literature that contains enormous information about the latest development in this field.

Administration, Inhalation↗
PubMed1996

Acute effects of inhaled and i.v. cocaine on airway dynamics.

BACKGROUND: Wheezing has been reported by 32% of habitual smokers of crack cocaine, and several cases of crack-related acute exacerbations of asthma have been reported. STUDY OBJECTIVE: To compare the acute effects of physiologically active doses of smoked cocaine base and, i.v. cocaine hydrochloride (HCl), a subphysiologic dose of cocaine base (smoked "placebo"), and i.v. saline solution placebo on bronchomotor tone, subjective level of intoxication, and cardiovascular responses in healthy habitual crack users. DESIGN: A single-blind crossover study in which the order of route of administration (inhaled vs i.v.) was random but placebo always preceded the active drug. SUBJECTS: Fourteen healthy, nonasthmatic current crack-smoking subjects, 34 to 48 years of age, with a history of previous i.v. cocaine use (1 to 12 times per lifetime). METHODS: Heart rate, BP, self-rated level of intoxication (scale of 0 to 10), and measurements of airway resistance (Raw) and specific airway conductance (SGaw) were recorded during separate sessions before and 3 to 5, 10, 15, and 30 min after administration of smoked cocaine base (38.5 +/- 2.3 [SEM] mg), smoked placebo (2.3 +/- 0.9 mg cocaine base), i.v. cocaine HCl (30.0 +/- 2.0 mg), and i.v placebo (saline solution). RESULTS: Both smoked active cocaine and i.v. cocaine HCl caused comparable, significant (p < 0.05) peak levels of acute intoxication (6.7 +/- 0.7 and 7.3 +/- 0.8, respectively) and increases in heart rate from baseline (29.6 +/- 2.9% and 21.4 +/- 3.7%, respectively, at 5 min). However, only smoked active cocaine caused significant decreases from baseline in SGaw (25.4 +/- 6.3% at 5 min), in contrast to nonsignificant changes after i.v. cocaine HCl (5.6 +/- 7.0% increase) and smoked placebo (10.2 +/- 6.0% decrease). CONCLUSIONS: Smoked cocaine base, but not systemically administered cocaine HCl, causes acute bronchoconstriction that is probably mediated by local airway irritation and could account for reports of crack-induced wheezing and asthma attacks in nonasthmatic and asthmatic individuals, respectively.

Administration, Inhalation↗
PubMedDate not supplied

The comparison of the effects of fluticasone propionate and budesonide on clinical indices and on bone mineral density in the asthmatic patients: a one year treatment study.

BACKGROUND: it is well accepted that the inhaled administration of steroids is efficacious and has fewer side effects than the systemic use. Among them fluticasone propionate (FP) has been said to cause the similar antiasthma effect without unfavorable side effect at half the dose of the other ICS. The aim of the study was to compare the effects of FP 500 microg/day and budesonide (BUD) 800 microg/day as a pressurized metered dose inhaler (pMDI) for one year on clinical indices determined by FEV1 and diurnal variation of PEFR (peak expiratory flow rates) and on laboratory indices determined by serum cortisol and bone mineral density (BMD). METHODS: a total of 30 nonsmoking mild to moderate asthmatic patients were recruited the study. 15 patients were given 800 microg/day BUD and 15 patients were given 500 microg/day FP as a pMDI. BMD measurements were done with dual energy X-ray absorbtiometry (DEXA) before and after the treatment at the lumbar area of the spine (L1-4) and left hip (trocanter major, neck of femur, intertrocanteric region and Ward's triangle). 10 patients of BUD group and 13 of FP group completed the study. After a year of treatment period, patients were compared on the basis of clinical indices (FEV1 and variability of PEFR), on serum cortisol levels and on BMD in both groups. RESULTS: after the treatment, variability of PEFR (in BUD group p < 0,01, in FP group p < 0,001) and FEV1 (in BUD group p < 0,05, in FP group p < 0,05) were both improved in the groups. Serum cortisol levels and BMD of the patients in both groups were not changed significantly (p > 0,05). CONCLUSIONS: the results suggested that FP 500 microg/d and BUD 800 microg/d as a pMDI results in a similar antiasthma effect without causing any adverse effect on BMD in mild and moderate asthmatics after one year treatment period.

Administration, Inhalation↗
PubMed2006

Inhaled delivery of aerosolized cyclosporine.

Aerosolized cyclosporine was the first calcineurin inhibitor to be developed for inhaled administration. Its use as a topical immunosuppressant after lung transplantation is reviewed. Animal studies in transplant and non-transplant models are considered, as is nebulized delivery of the drug, including the results of scintigraphy and pharmacokinetic studies. Open label clinical studies of the drug for the treatment of chronic and acute lung transplant rejection are detailed. Placebo controlled trials for rejection prophylaxis are described and future directions for the drug are considered. Aerosol cyclosporine provides an excellent example of how inhaled aerosol delivery can provide therapeutic concentrations of drug in the lungs while minimizing the side effects associated with high systemic concentrations. In the case of lung transplantation, the drug is delivered directly to the airways, the location of the pathology resulting in most mortality in this population (chronic allograft rejection), maximizing the efficacy of this dose-dependent immunosuppressant.

Administration, Inhalation↗
PubMed1999

Inhaled nitric oxide does not improve cardiac or pulmonary function in patients with an exacerbation of chronic obstructive pulmonary disease.

OBJECTIVE: To determine whether inhaled nitric oxide (NO) improves right ventricular function in mechanically ventilated patients with severe chronic obstructive pulmonary disease (COPD). DESIGN: Open, prospective, controlled trial. SETTING: General intensive care unit of a community hospital. PATIENTS: Twelve patients with acute respiratory failure caused by acute exacerbation of COPD requiring mechanical ventilation. INTERVENTIONS: Insertion of a pulmonary artery catheter modified with a rapid response thermistor and a radial arterial catheter. Nitric oxide was then administered to the patient via a T piece placed between the Y piece of the ventilator and the endotracheal tube. MEASUREMENTS AND MAIN RESULTS: Hemodynamic and gasometric variables were recorded before NO inhalation, during administration of inhaled NO (20 ppm, 20 mins), and 20 mins after NO discontinuation. Inhaled NO reduced pulmonary artery pressure from 26 +/- 6 to 22 +/- 5 mm Hg (p = .0004), but arterial oxygenation, cardiac output, and right ventricular ejection fraction remained unmodified (41% +/- 9% vs. 41% +/- 8%; not significant). Calculated pulmonary vascular resistance decreased from 453 +/- 233 to 348 +/- 108 dyne x sec/cm5 x m2 (p = .02), and right ventricular volumes did not change. Subsequently, right ventricular end-systolic pressure/volume ratio decreased from 0.52 +/- 0.22 to 0.44 +/- 0.19 mm Hg/mL/m2 (p = .01). No significant correlation was observed between the changes of pulmonary artery pressure (or pulmonary vascular resistance) and changes of right ventricular ejection fraction. CONCLUSION: Inhalation of NO does not seem to improve either right ventricular function or arterial oxygenation in patients with acute respiratory failure caused by acute exacerbation of COPD.

Administration, Inhalation↗
PubMed2006

A new small volume holding chamber for asthmatic children: comparison with Babyhaler spacer.

When a new holding chamber for administrating inhaled medication is to be marketed, it needs to be compared with existing chambers with two questions in mind: is this chamber well accepted by patients and is there an in vitro equivalence? We compared the new small volume non-electrostatic valved holding chamber, usable with all pressurized metered-dose inhalers and equipped with a funny facemask, Vortex (Pari GmbH, Germany), to the most frequently prescribed holding chamber in France, Babyhaler (GlaxoSmithKline Laboratories). Preferences were studied for 75 families with a child no more than 4 yr old, using standard questionnaires. An in vitro study assessed the delivered dose and the particle size distribution of two HFA beclomethasone dipropionate pressurized metered dose inhalers (Becotide 250 microg per dose and Nexxair 100 microg per dose) by dose uniformity sample apparatus and cascade impactor according to the European Pharmacopoeia. Vortex was preferred by 95% of the families because of its small size, its duck facemask, and its robust appearance. Among children able to give their opinion, 86% preferred Vortex to Babyhaler. In vitro, both holding chambers reduced the delivered dose of beclomethasone dipropionate and increased the quantity of particles smaller than 5 microm in diameter with both medications. A higher proportion of fine particles was obtained with Nexxair than with Becotide (p < 0.05) and with Vortex than with Babyhaler (p < 0.05). As expected, throat deposition is dramatically reduced for both drugs with both holding chambers. The in vitro difference in the particle size distribution of beclomethasone dipropionate with both holding chambers probably has no clinical influence.

Administration, Inhalation↗
PubMed2002

Enhanced insulin absorption in the rabbit airways and lung by sodium dioctyl sulfosuccinate.

The objective of this investigation was to study regional absorption of inhaled insulin together with an enhancer (sodium di-octyl-sulfosuccinate [DOSS]) in the rabbit airways and lung. Insulin was administered with or without DOSS by aerosol inhalation, intratracheal infusion, intranasally, sublingually, and without DOSS intravenously. Blood glucose and plasma levels of insulin were measured during 100 min from the start of administration. Inhalation of insulin (3 U) with 0.25% or 1% DOSS decreased average blood glucose levels significantly more than inhalation of insulin (3 U) without DOSS. Intratracheal administration of 1.5 U of insulin with 0.25% DOSS in 0.3 mL of vehicle decreased the average blood glucose level significantly compared with intratracheal administration of 1.5 U of insulin and no DOSS in 0.3 mL of vehicle and compared with 1.5 U of insulin with 0.25% DOSS in 0.15 mL of vehicle. Intravenous insulin (1.5 U) and inhaled (1.5 U) insulin in 0.25% DOSS decreased average blood glucose levels significantly compared with intratracheal (0.15 mL), intranasal, and sublingual administration of 1.5 U of insulin with 0.25% DOSS. The bioavailability of inhaled insulin (1.5 U) with 0.25% DOSS was estimated to be 16% in comparison with 7% for intratracheally (0.15 mL), 1% intranasally, and 0.8% sublingually administered insulin (1.5 U with 0.25% DOSS), respectively. Inhaled insulin together with the absorption enhancer DOSS decreased the blood glucose level more effectively than insulin given intratracheally, intranasally, or sublingually. The effect on blood glucose reflected the difference in plasma insulin concentration for the different routes of administration.

Absorption↗
PubMed1998

Clodronate is effective in preventing corticosteroid-induced bone loss among asthmatic patients.

Clodronate is a novel drug used for inhibiting osteoclastic activity. The aim of the present double-blind study was to evaluate the efficacy and tolerability of clodronate (Leiras, Finland) in corticosteroid-induced bone loss among asthmatic patients. Seventy-four adult patients (41 women and 33 men, mean age 57.3 years) having a long history (mean 8.1 years) of oral and inhaled corticosteroid therapy were randomized to four parallel treatment groups: clodronate 800, 1600, or 2400 mg/day, or an identical placebo. The bone mineral density (BMD) of the lumbar spine (L2-4), femoral neck, and trochanter were assessed using dual-energy X-ray absortiometry at entry, 6 months, and 12 months. The baseline BMDs did not differ significantly between the study groups. In the lumbar spine, the mean BMD increased significantly between the baseline and 12-month visit in the clodronate groups of 1600 and 2400 mg/day, 2.6% (0.02 g/cm2, p < 0.02) and 3.0% (0.03 g/cm2, p < 0.01), respectively, but not in the placebo and clodronate 800 mg/day groups. The test for a linear trend (BMD percent change for L2-4) at 12 months was significant (p < 0.02), indicating a dose response to clodronate. The mean BMD values of the femoral neck increased significantly in the 2400 mg/day group, 4.3% (0.03 g/cm2, p < 0.0001), as well as in the trochanter region 2.8% (0.02 g/cm2, p < 0.02). Gastric irritation was the most common adverse effect noted on a clodronate dose of 2400 mg/day. We conclude that oral clodronate is effective in preventing bone loss or increasing bone mass in asthmatic patients having a long history of continuous peroral and inhaled corticosteroid administration.

Absorptiometry, Photon↗
PubMedDate not supplied

The effects of the nitric oxide synthase inhibitor 7-nitroindazole on ethanol pharmacokinetics in rats after acute and chronic ethanol administration.

The aim of this work was to study the effects of the nitric oxide synthase (NOS) inhibitors 7-nitroindazole (7-NI) and NG-nitro-L-arginine (L-NOARG) on the effects and pharmacokinetics of ethanol in rats. Ethanol at a dose of 4 g/kg, i.p. induced sleep in rats (sleep time: 117.2+/-30.7 min). Administration of the NOS inhibitors 7-NI (20 mg/kg, i.p.) and L-NOARG (20 mg/kg, i.p.) 30 min before ethanol significantly increased the duration of ethanol-induced sleep. L-NOARG also significantly increased the toxicity of ethanol as evidenced by increased post-experimental lethality. Ethanol at a dose of 2 g/kg (i.p.) did not induce sleep in vehicle-treated rats; however, the combined administration of ethanol (2 g/kg) and 7-NI at doses of 40, 80, and 120 mg/kg caused sleep, for 49.4+/-3.7, 204.0+/-13.3, and 447.5+/-62.8 min, respectively. L-NOARG (20 mg/kg) had no effect on ethanol concentrations in blood after acute ethanol administration (4 g/kg). 7-NI in lower doses (20 and 40 mg/kg) had no effect and in higher doses (80 and 120 mg/kg) significantly slowed ethanol clearance during the 12 h after ethanol administration. The effect of 7-NI (20 mg/kg) on ethanol pharmacokinetics after chronic ethanol administration (inhalation for 18 days) was also studied. The administration of 7-NI immediately after the end of ethanol exposure had a pronounced effect on ethanol pharmacokinetics; in 7-NI-treated rats the fall in ethanol concentrations was significantly slower as compared with vehicle-treated rats. In 7-NI-treated rats, blood-ethanol levels were higher at 3, 6, 9, and 12 h after the end of ethanol exposure.

Animals↗