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Revue Francaise Des Maladies... 1980
Topics: Administration, Oral; Almitrine; Humans; Infusions, Parenteral; Kinetics; Lung Diseases, Obstructive; Piperazines
PubMed: 7291691
DOI: No ID Found -
Journal of Applied Physiology... Jul 1985Almitrine increases breathing by stimulating peripheral chemoreceptors. Previous studies suggest clinical usefulness in the adult with chronic obstructive pulmonary... (Comparative Study)
Comparative Study
Almitrine increases breathing by stimulating peripheral chemoreceptors. Previous studies suggest clinical usefulness in the adult with chronic obstructive pulmonary disease, but little data are available to decide whether almitrine would be helpful in diseases involving pharyngeal airway obstruction, such as apnea of prematurity or obstructive sleep apnea. We investigated the effect of intravenous almitrine on hypoglossal (HG), an upper airway nerve, and phrenic (PHR) neural activity in eight alpha-chloralose-urethan anesthetized, paralyzed, vagotomized, and artificially ventilated cats. Recordings were made of raw and integrated HG and PHR electroneurograms (ENGs), alveolar PCO2, arterial PO2, arterial blood pressure, and rectal temperature. A dose-response study of cumulative almitrine doses ranging from 0.1 to 4.0 mg/kg was performed in three cats. The interactive effects of almitrine and hypoxic stimulation were investigated in four cats. The interactive effects of almitrine and hypercapnic stimulation were investigated in five cats. The interactive effects of almitrine and ventilatory timing were investigated in six cats. We found that 1) almitrine doses as low as 0.1 mg/kg iv increased both HG and PHR ENG activity, with a maximum effect at approximately 1.0 mg/kg; 2) almitrine markedly increased HG and PHR ENG activity at all arterial PO2 values from 35-175 Torr; 3) almitrine increased HG and PHR ENG activity at all arterial PCO2 values from 30-70 Torr; and 4) almitrine increased the ratio of tidal volume to inspiratory time and decreased the inspiratory muscle duty cycle at normoxia and eucapnia.
Topics: Airway Obstruction; Almitrine; Animals; Arteries; Carbon Dioxide; Cats; Dose-Response Relationship, Drug; Electrophysiology; Female; Hypoglossal Nerve; Male; Oxygen; Partial Pressure; Phrenic Nerve; Piperazines; Respiration; Time Factors
PubMed: 3928579
DOI: 10.1152/jappl.1985.59.1.105 -
Anesthesiology Oct 1987The effect of almitrine bismesylate on the hypoxic pulmonary vasoconstrictor (HPV) response was studied in seven closed-chest dogs anesthetized with pentobarbital and...
The effect of almitrine bismesylate on the hypoxic pulmonary vasoconstrictor (HPV) response was studied in seven closed-chest dogs anesthetized with pentobarbital and paralyzed with pancuronium. The right lung was ventilated continuously with 100% O2, while the left lung was ventilated with either 100% O2 ("hyperoxia") or with an hypoxic gas mixture ("hypoxia": end-tidal PO2 = 50.1 +/- 0.1 mmHg). Cardiac output (CO) was altered from a "normal" value of 3.10 +/- 0.18 l . min-1 to a "high" value of 3.92 +/- 0.16 l . min-1 by opening arteriovenous fistulae which allowed measurements of two points along a pressure-flow line. These four phases of left lung hypoxia or hyperoxia with normal and high cardiac output were repeated in the presence and absence of almitrine. Almitrine bismesylate was administered as a constant infusion of 14.3 micrograms . kg-1 . min-1 for a mean plasma concentration of 219.5 +/- 26.4 ng . ml-1. Relative blood flow to each lung was measured with a differential CO2 excretion (VCO2) method corrected for the Haldane effect. With both lungs hyperoxic, the percent left lung blood flow (%QL-VCO2) was 44 +/- 1%. When the left lung was exposed to hypoxia, the %QL-VCO2 decreased significantly to 22 +/- 1%. However, with the administration of almitrine, the %QL-VCO2 during left lung hypoxia increased significantly to 36 +/- 2%. The arterial oxygen tension decreased significantly between hyperoxia (PaO2 = 633 +/- 6 mmHg) and hypoxia (271 +/- 31 mmHg). With the addition of almitrine, there was no change during hyperoxia; however, during hypoxia, the PaO2 decreased significantly to 124 +/- 15 mmHg. Cardiac output did not influence these findings. The pulmonary vascular conductance (G) is the slope of the pressure-flow line.(ABSTRACT TRUNCATED AT 250 WORDS)
Topics: Almitrine; Animals; Central Nervous System Stimulants; Dogs; Female; Hypoxia; Lung; Piperazines; Vasoconstriction
PubMed: 2889404
DOI: 10.1097/00000542-198710000-00015 -
European Journal of Clinical... 1989The absorption of almitrine from the upper gastrointestinal tract has been evaluated in 6 healthy volunteers by an intubation technique. Almitrine bismesylate dissolved...
The absorption of almitrine from the upper gastrointestinal tract has been evaluated in 6 healthy volunteers by an intubation technique. Almitrine bismesylate dissolved in malic acid was introduced into the stomach after homogenization with a meal containing the marker 14C-polyethylene glycol (PEG) 4000. Unlabeled PEG 4000 was infused into the second part of duodenum throughout the experiment. Samples of the luminal content were collected every 15 min for four hours from the stomach and at the ligament of Treitz. Blood was also collected. Almitrine was neither absorbed from nor metabolized in the stomach. About 37% of the quantity of drug emptied from the stomach was absorbed from the duodenum. Almitrine was detected in plasma 50 min after ingestion of the meal and its plasma concentration-time profile reflected the cumulative gastric emptying rate. The metabolite tetrahydroxy almitrine was found in intestinal samples as soon as unchanged drug was detected in plasma. The intraluminal rate of formation of the metabolite increased with time. The results suggest hepatic metabolism of almitrine followed by rapid excretion of the metabolite in the bile.
Topics: Adult; Almitrine; Digestive System; Humans; Intestinal Absorption; Intubation, Gastrointestinal; Male
PubMed: 2598987
DOI: 10.1007/BF00558129 -
Chest May 1994Assessment of acute and chronic effects of low-dose almitrine bismesylate (AB) in stable chronic obstructive pulmonary disease (COPD). (Clinical Trial)
Clinical Trial
STUDY OBJECTIVE
Assessment of acute and chronic effects of low-dose almitrine bismesylate (AB) in stable chronic obstructive pulmonary disease (COPD).
STUDY DESIGN
Oral administration of AB, 25 mg three times a day, for 6 months in all patients. Pulmonary function, blood gases, and peripheral nerve conduction velocity were measured at baseline and after long-term administration of AB. In addition, oral pharmacokinetics and effects on pulmonary circulation at rest were studied in half of the patients. Intravenous pharmacokinetics were measured after a single intravenous dose of 60 mg of AB 3 months before the start of oral AB treatment in the other seven patients.
SETTING
Outpatient clinic of a community hospital in a coal mining district in southwest Germany.
PATIENTS
Fourteen patients with clinically stable COPD and hypoxemia.
RESULTS
Acute effects of AB were as follows: a significant increase in arterial oxygen tension (PaO2) from 61 +/- 7 mm Hg to 74 +/- 8 mm Hg (p < 0.001), a decrease in arterial carbon dioxide tension (PaCO2) from 41 +/- 8 mm Hg to 38 +/- 7 mm Hg (p < 0.01), a rise of pH from 7.45 +/- 0.04 to 7.48 +/- 0.04 (p < 0.01), and a transient increase in mean pulmonary artery pressure from 26 +/- 7 to 29 +/- 6 mm Hg (not significant). After long-term treatment, once tissues were saturated with almitrine, improvement in gas exchange persisted with a PaO2 of 70 +/- 10 mm Hg (p < 0.001) and a PaCO2 of 39 +/- 6 mm Hg (not significant) without elevation of pH (7.45 +/- 0.04) or of pulmonary artery pressure (26 +/- 8 mm Hg). The terminal half-life of AB was 56 +/- 45 days after a single intravenous administration, and 55 +/- 16 days after long-term oral dosing. None of the patients developed clinically manifest peripheral neuropathy. Impaired asymptomatic peripheral motor nerve function was prevalent in 4 (29 percent) of the patients and remained unchanged during long-term AB administration. However, asymptomatic impairment of motor nerve conduction velocity developed in two patients with inadequate high AB plasma levels despite low-dose therapy. Both patients were known to have additional conditions predisposing for neuropathy.
CONCLUSIONS
Low-dose AB therapy, 75 mg daily, resulted in sustained elevation of arterial oxygen tension in hypoxemic patients with COPD. Although pulmonary artery pressure increased transiently after the first dose, it remained unchanged with long-term treatment despite persistent improvement of pulmonary gas exchange.(ABSTRACT TRUNCATED AT 250 WORDS)
Topics: Administration, Oral; Aged; Almitrine; Carbon Dioxide; Female; Humans; Hypoxia; Infusions, Intravenous; Lung Diseases, Obstructive; Male; Middle Aged; Oxygen; Respiratory Mechanics
PubMed: 8181324
DOI: 10.1378/chest.105.5.1383 -
Annales Francaises D'anesthesie Et de... 1988
Topics: Almitrine; Buprenorphine; Central Nervous System Stimulants; Humans; Piperazines; Respiratory Insufficiency
PubMed: 2896478
DOI: 10.1016/s0750-7658(88)80153-9 -
American Journal of Respiratory and... Dec 1998Inhaled nitric oxide (iNO), a selective pulmonary vasodilator and intravenously administered almitrine, a selective pulmonary vasoconstrictor, have been shown to...
Inhaled nitric oxide (iNO), a selective pulmonary vasodilator and intravenously administered almitrine, a selective pulmonary vasoconstrictor, have been shown to increase PaO2 in patients with acute respiratory distress syndrome (ARDS). This prospective study was undertaken to assess the cardiopulmonary effects of combining both drugs. In 48 consecutive patients with early ARDS, cardiorespiratory parameters were measured at control, after iNO 5 ppm, after almitrine 4 micrograms. kg-1. min-1, and after the combination of both drugs. In 30 patients, dose response to 2, 4, and 16 micrograms. kg-1. min-1 of almitrine with and without NO was determined. Almitrine and lactate plasma concentrations were measured in 17 patients. Using pure O2, PaO2 increased by 75 +/- 8 mm Hg after iNO, by 101 +/- 12 mm Hg after almitrine 4 micrograms. kg-1. min-1, and by 175 +/- 18 mm Hg after almitrine combined with iNO (p < 0.001). In 63% of the patients, PaO2 increased by more than 100% with the combination of both drugs. Mean pulmonary artery pressure (Ppa) increased by 1.4 +/- 0.2 mm Hg with almitrine 4 micrograms/kg/ min (p < 0.001) and decreased by 3.4 +/- 0.4 mm Hg with iNO and by 1.5 +/- 0.3 mm Hg with the combination (p < 0.001). The maximum increase in PaO2 was obtained at almitrine concentrations <= 4 micrograms. kg-1. min-1, whereas almitrine increased Ppa dose-dependently. Almitrine plasma concentrations also increased dose-dependently and returned to values close to zero after 12 h. In many patients with early ARDS, the combination of iNO 5 ppm and almitrine 4 micrograms. kg-1. min-1 dramatically increases PaO2 without apparent deleterious effect allowing a rapid reduction in inspired fraction of O2. The long-term consequences of this immediate beneficial effect remain to be determined.
Topics: Administration, Inhalation; Almitrine; Analysis of Variance; Blood Pressure; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Follow-Up Studies; Heart; Humans; Injections, Intravenous; Lactates; Lung; Male; Middle Aged; Nitric Oxide; Oxygen; Positive-Pressure Respiration; Prospective Studies; Pulmonary Artery; Respiratory Distress Syndrome; Respiratory System Agents; Shock, Septic; Vascular Resistance; Vasoconstrictor Agents; Vasodilator Agents
PubMed: 9847266
DOI: 10.1164/ajrccm.158.6.9804066 -
Praxis Und Klinik Der Pneumologie Jun 1988
Review
Topics: Almitrine; Central Nervous System Stimulants; Hemodynamics; Humans; Lung Diseases, Obstructive; Piperazines; Pulmonary Circulation
PubMed: 2902612
DOI: No ID Found -
European Journal of Pharmacology Jan 2001The effects of almitrine on the contractile properties of isolated geniohyoid and sternohyoid muscles were determined in physiological salt solution at 30 degrees C in...
The effects of almitrine on the contractile properties of isolated geniohyoid and sternohyoid muscles were determined in physiological salt solution at 30 degrees C in young and old rats. In young rats, almitrine had no effect on twitch or tetanic tension, twitch:tetanic tension ratio, contractile kinetics, active or passive tension-length relationships or frequency-tension relationship in both muscles. Almitrine significantly increased resistance to fatigue in both muscles. In old rats, almitrine had no effect on twitch or tetanic tension, twitch:tetanic tension ratio, contractile kinetics, active or passive tension-length relationships, frequency-tension relationship or fatigue in both muscles. These results show that almitrine, in both young and old rats, has no effect on most of the contractile properties of isolated geniohyoid and sternohyoid muscles. However, almitrine increases resistance to fatigue in both muscles in young but not in old rats.
Topics: Age Factors; Almitrine; Animals; Muscle Contraction; Rats; Rats, Wistar; Respiratory Muscles; Respiratory System Agents
PubMed: 11165230
DOI: 10.1016/s0014-2999(01)00721-x -
European Journal of Respiratory... 1983Almitrine bismesylate 100 mg orally was given to eight patients with severe chronic obstructive pulmonary disease (COPD). In five patients, gasometric, haemodynamic and...
Almitrine bismesylate 100 mg orally was given to eight patients with severe chronic obstructive pulmonary disease (COPD). In five patients, gasometric, haemodynamic and lung mechanics parameters, and almitrine plasma levels were measured at baseline and every hour up to five hours after almitrine bismesylate intake. Maximal almitrine plasma levels were reached after 2 hours (89 +/- 41 ng/ml, mean +/- SEM) and persisted up to the fifth hour (68 +/- 25 ng/ml). Pulmonary vascular resistance increased significantly from baseline 433 +/- 120 dynes.s.cm-5 to 503 +/- 124, p less than 0.05 at the second hour and to 509 +/- 119, p less than 0.05 at the fifth hour. Arterial oxygen saturation increased significantly from baseline 81.7 +/- 4.9% to 84.5 +/- 5.0, p less than 0.05 at the second hour and to 84.5 +/- 4.6, p less than 0.05 at the fifth hour. Venous admixture decreased significantly from baseline 35 +/- 9% to 30 +/- 9, p less than 0.05 at the second hour and to 28 +/- 9, p less than 0.01 at the fifth hour. Pulmonary artery mean pressure, cardiac output and minute ventilation did not change. The continuous distributions of ventilation-perfusion ratios (VA/Q), using the multiple inert gas elimination technique, were determined in six patients, at baseline and two hours after almitrine bismesylate intake. An improvement in VA/Q matching was observed after almitrine with a diversion of an average of 15 per cent of total blood flow from hypoxic units (VA/Q between 0.08 and 0.4) to normoxic units (VA/Q between 0.5 and 1.8).(ABSTRACT TRUNCATED AT 250 WORDS)
Topics: Aged; Almitrine; Female; Humans; Lung Diseases, Obstructive; Male; Middle Aged; Piperazines; Pulmonary Gas Exchange; Ventilation-Perfusion Ratio
PubMed: 6586439
DOI: No ID Found