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PubMed1985

Spacer devices used with metered-dose inhalers. Breakthrough or gimmick?

In an effort to improve the delivery of a drug to the lungs, to correct problems of hand-lung discoordination, and to reduce local side effects such as oral candidiasis, a number of spacer devices have been developed to attach to metered-dose inhalers. Administration of bronchodilator drugs to patients with faulty techniques of inhalation has been improved with the addition of spacers. In adults and older children with a correct technique of inhaling bronchodilators, the spacer devices do not seem to have any advantage over the simple metered-dose inhalers. Young children (two to five years) can benefit from inhaled bronchodilators or corticosteroids by use of spacer devices with one-way valves. Older children and especially adults who suffer from dysphonia or thrush from inhaled corticosteroids can also benefit from spacers. In patients whose condition is well controlled with the usual inhaled doses of corticosteroids with no local side effects, spacer devices show promise, but more studies are needed.

Administration, Topical↗
PubMed1999

Pharmacokinetics of zanamivir after intravenous, oral, inhaled or intranasal administration to healthy volunteers.

OBJECTIVE: The objective of these studies was to examine the clinical pharmacokinetics and safety of zanamivir, an influenza A and B virus neuraminidase inhibitor, when administered to healthy volunteers. DESIGN: The safety, tolerability and pharmacokinetics of zanamivir administered by a number of routes were assessed in randomised, double-blind and placebo-controlled studies. The study of absolute oral bioavailability had an open design. STUDY PARTICIPANTS: The participants in these studies were healthy male or female volunteers. INTERVENTIONS: Zanamivir was administered as single or multiple doses by the intravenous, oral, inhaled (nebuliser and dry powder) and intranasal routes. Serum and urine samples were obtained for determination of pharmacokinetic parameters, and nasal washes and throat gargles were performed to assess drug concentrations in the nose and throat. Safety was evaluated by monitoring adverse events, vital signs and laboratory parameters. RESULTS: Zanamivir was well tolerated at all doses by all routes; no serious adverse events were reported. The kinetics of zanamivir were linear with single intravenous doses up to 600 mg, and there was no evidence of modification in the kinetics after repeated twice-daily administration. Approximately 90% of zanamivir was excreted unchanged in the urine. The elimination of zanamivir from the serum was a first-order process with a half-life of approximately 2 hours and, at 16 L, the volume of distribution was similar to that of extracellular water. The absolute oral bioavailability of zanamivir was low, averaging 2%. After intranasal or oral inhaled administration, a median of 10 to 20% of the dose was systemically absorbed, with maximum serum concentrations generally reached within 1 to 2 hours. The median serum half-life ranged between 2.5 and 5.05 hours, suggesting that the elimination rate is limited by absorption. There was no evidence of modification in the kinetics after repeated inhaled administration. CONCLUSIONS: Zanamivir is a well tolerated drug. The low level of absorption of the drug after inhaled administration results in low serum concentrations, and therefore there is modest systemic exposure to zanamivir after inhalation. Zanamivir is not metabolised, and the potential for clinically relevant drug-drug interactions is very low.

Administration, Inhalation↗
PubMed1992

Bronchodilator action of inhaled nitric oxide in guinea pigs.

The effects of inhaling nitric oxide (NO) on airway mechanics were studied in anesthetized and mechanically ventilated guinea pigs. In animals without induced bronchoconstriction, breathing 300 ppm NO decreased baseline pulmonary resistance (RL) from 0.138 +/- 0.004 (mean +/- SE) to 0.125 +/- 0.002 cmH2O/ml.s (P less than 0.05). When an intravenous infusion of methacholine (3.5-12 micrograms/kg.min) was used to increase RL from 0.143 +/- 0.008 to 0.474 +/- 0.041 cmH2O/ml.s (P less than 0.05), inhalation of 5-300 ppm NO-containing gas mixtures produced a dose-related, rapid, consistent, and reversible reduction of RL and an increase of dynamic lung compliance. The onset of bronchodilation was rapid, beginning within 30 s after commencing inhalation. An inhaled NO concentration of 15.0 +/- 2.1 ppm was required to reduce RL by 50% of the induced bronchoconstriction. Inhalation of 100 ppm NO for 1 h did not produce tolerance to its bronchodilator effect nor did it induce substantial methemoglobinemia (less than 2%). The bronchodilating effects of NO were additive with the effects of inhaled terbutaline, irrespective of the sequence of NO and terbutaline administration. Inhaling aerosol generated from S-nitroso-N-acetylpenicillamine also induced a rapid and profound decrease of RL from 0.453 +/- 0.022 to 0.287 +/- 0.022 cmH2O/ml.s, which lasted for over 15 min in guinea pigs broncho-constricted with methacholine. Our results indicate that low levels of inhaled gaseous NO, or an aerosolized NO-releasing compound are potent bronchodilators in guinea pigs.

Aerosols↗
PubMed2004

Heroin use among female adolescents: the role of partner influence in path of initiation and route of administration.

This study examined heroin initiation and route of administration among 16 female adolescents in the greater Baltimore Metropolitan area. Participants were more than twice as likely to be introduced to heroin by a male friend or boyfriend (IHM) than introduced to heroin by other means (IHO). The majority of IHM females were introduced by a male friend rather than a romantic partner. No relationship was found between path of initiation (IHM, IHO) and initial route of administration (inhalation, smoking, injecting) or history of injection (ever injected, never injected). The effect of opposite-gender peer influence in the initiation of female adolescent heroin use is discussed along with how the current findings may influence treatment and prevention efforts. A statistically significant relationship was found for initial route of administration and for history of injection. Ninety-four percent of participants reported initiation of heroin use by inhalation, while an alarming 75% of participants reported injecting heroin at some time during their history of use. Participants were no more likely to be introduced to injection by a boyfriend or male friend than by other means. The finding that the majority of females first try heroin through inhalation is consistent with an increased use of heroin by this method among young people in recent years. However, the majority of users in this study used heroin through injection at least once in their addict career, a route of administration associated with increased health and safety risks. Potential explanations for the progression from snorting to injection are presented as well as implications for the delivery of prevention and treatment services.

Administration, Inhalation↗
PubMed1988

Use of ipratropium bromide in obstructive lung disease.

The chemistry, pharmacology, pharmacokinetics, clinical efficacy, adverse effects, and dosage of ipratropium bromide are reviewed. Ipratropium bromide, a synthetic quaternary isopropyl derivative of atropine, interrupts vagally mediated bronchoconstriction by inhibiting the cyclic guanosine 3',5'-monophosphate system at parasympathetic nerve endings. Ipratropium bromide is poorly absorbed after oral and inhaled administration but diffuses rapidly into tissue after i.v. or i.m. administration. The elimination half-life is 3.2-3.8 hours. After inhalation, the drug is eliminated in the urine and feces. The bronchodilatory effect of ipratropium bromide in stable chronic obstructive pulmonary disease appears to be comparable, and may be superior, to that of the beta-sympathomimetic agents. In acute exacerbations, ipratropium bromide is useful but may not be the preferred agent because of a delayed onset of action (within 15 minutes; mean dose-dependent duration of effect, three to five hours). Combination therapy with other bronchodilating drugs has proved useful. Ipratropium bromide may be a useful adjunctive agent in the treatment of asthma. Since the onset of action is delayed, ipratropium bromide should not be used as single-drug therapy in an acute asthmatic exacerbation. Reported adverse effects, including cough, nausea, palpitations, dry mouth, nervousness, gastrointestinal distress, and dizziness, have been mild. The usual dosage is two inhalations (36 micrograms) four times daily, and the maximum number of doses per day should not exceed 12. Although ipratropium bromide is currently indicated only for maintenance therapy in stable chronic bronchitis and emphysema, it may be useful as adjunctive therapy in asthma and in the management of acute exacerbations of chronic bronchitis and asthma. Additional experience in a variety of chronic obstructive pulmonary disorders will help to clarify the role of ipratropium bromide in the treatment of obstructive pulmonary disease.

Asthma↗
PubMed1998

Bronchodilators and corticosteroids in the treatment of asthma.

Despite advancements in treatment, the incidence of asthma, asthma-related deaths and hospitalizations for asthma have increased significantly during the past decade. Although asthma mortality may now be decreasing, reasons for the worsening of morbidity and mortality in asthma remain unclear. These unexpected changes in asthma severity have sparked renewed interest in research into the pathogenesis and treatment of the condition. Beta(2)-Adrenergic agonists are the most commonly used class of drugs for the treatment of asthma. Recent concerns about safety issues for beta-agonists caused reevaluation of prescribing practices, and using them on an as-needed basis is now more frequently accepted and recommended. In acute asthma, a beta(2)-adrenergic agonist is still the medication of choice. Long-acting salmeterol and formoterol, administered only twice daily, can decrease symptoms of asthma during day and nighttime. On the other hand, the role of tolerance to their bronchodilator and bronchoprotective effects is still to be determined in the treatment of asthma. Theophylline, whose use has been limited by the potential for serious toxicity, may regain an important position in asthma treatment with the development of the knowledge about its antiinflammatory actions. Dosing theophylline on a time- related basis also improves the risk/benefit ratio and makes it a useful drug for nocturnal asthma. Ipratropium bromide, an anticholinergic drug, still awaits a defined role in the treatment of asthma. Studies on its use for acute asthma have not achieved consensus and, for nocturnal asthma, the short duration of effect limits the benefits. Corticosteroids, including inhaled steroids, have measurable effects on symptoms, lung function, bronchial responsiveness and inflammation associated with asthma. Side effects of chronic use limit systemic, but not inhaled administration. Newer preparations, like budesonide, flunisolide and fluticasone, decrease the incidence of possible side effects related to inhaled steroids by having better ratio of topical to systemic potency. Daily doses up to 1600 micro g of beclomethasone (or equivalent) are considered safe and higher doses should be reserved for patients with moderate to severe asthma. Although future trials are necessary to clarify many issues related to dosing of inhaled steroids, chronotherapy studies have shown that single administration between 3 and 5:30 p.m. may be as effective as 4 times a day dosing.

Journal Article↗
PubMed2000

Effect of food and gender on the pharmacokinetics of RP 73401, a phosphodiesterase IV inhibitor.

OBJECTIVE: Early exploratory clinical pharmacokinetic studies can provide valuable information for the design and control of subsequent phase 2 studies. This philosophy was instituted for the compound RP 73401, a specific phosphodiesterase IV inhibitor, that was being developed simultaneously for delivery by both oral and pulmonary routes of administration. The objective of these studies was to separately evaluate the effect of food and gender on the pharmacokinetics of RP 73401 using small-scale focused pilot studies. METHODS: In the first study, 400 mcg of inhaled RP 73401 were administered to male and female healthy volunteers (n = 8 f, 8 m. In the second study, 400 mcg oral RP 73401 were administered to healthy male volunteers (n = 8) in the fed and fasted state in a crossover fashion. Serial plasma samples were collected for 24 hours and analyzed for RP 73401 using an HPLC method with post-column photochemical reaction and fluorescence detection that had a minimum quantifiable limit of 10 pg/ml. Pharmacokinetic parameters were calculated using non-compartmental techniques. RESULTS: Comparison of male and female pharmacokinetics following inhalation administration showed no statistically significant differences in the absorption and disposition of RP 73401 with respect to AUC, Cmax, tmax, and t1,2 values. Conversely, RP 73401 administered subsequently to a high fat meal showed a 51% reduction in Cmax and a 5-fold prolongation in tmax as compared to the fasted state. However, there was no statistically significant difference in the systemic availability of RP 73401 as assessed through AUC0-infinity comparisons. CONCLUSIONS: These results successfully allowed the uncomplicated inclusion of females in oral and inhalation studies with RP 73401 and indicated the need to address oral drug dosing conditions in order to minimize sources of pharmacokinetic variability in subsequent phase 2 studies.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1979

Pharmacology and toxicology of Atrovent.

The anticholinergic drug ipratropium bromide (Atrovent) can be described as having pharmacologically a high degree of activity and a certain bronchoselectivity when administered intravenously. Inhalation studies, however, indicate that this is the most suitable route of administration. Inhalation provides with small doses the most effective concentration locally at the smooth muscle of the airways without producing anticholinergic side effects due to absorption from the airways or from the gastrointestinal tract. In certain experimental models of allergic asthma, ipratropium bromide was shown to be capable of influencing favourably bronchoconstriction and mediator release. Extensive toxicological examinations revealed with high doses all typical symptoms of overdosing an anticholinergic drug, like mydriasis, dryness of the mucosae and meteorism with coprostasis. Acute and long term inhalation studies gave no evidence for a functional and morphological impairment of the lungs and airways.

Animals↗
PubMed1991

Pharmacodynamics, pharmacokinetics and safety profile of the new platelet-activating factor antagonist apafant in man.

Platelet-activating factor (PAF) is a unique phospholipid mediator with multifunctional properties. Evidence generated in experimental studies suggests that PAF plays a pathogenetic role in anaphylactic, inflammatory and immunogenic reactions. Apafant (WEB 2086, CAS 105219-56-5), a novel synthetic PAF receptor antagonist, was administered to a total of 101 healthy volunteers within 5 studies to investigate its pharmacologic activity, pharmacokinetic behaviour and safety profile. Pharmacologic activity was monitored by inhibition of 5 x 10(-8) mol/l PAF-induced platelet aggregation ex vivo. The following treatment schedules were studied: oral single dose 1.25 to 400 mg; oral multiple dose 100 mg t.i.d. over 7 days; i.v. infusion 0.5 to 50 mg (over 30 min); inhalative administration up to 1.0 mg. PAF induced platelet aggregation was virtually completely inhibited by single oral doses of 20 mg upwards, throughout during the multiple oral dose study, at all dose levels tested in the i.v. study and (significantly but not completely) at 0.5 and 1.0 mg in the inhalative study. Following oral administrations (capsules) apafant is absorbed rapidly (tmax 1 to 2 h), there is linear pharmacokinetics for the mean plasma concentrations of apafant measured by RIA as well as for the areas under the curve (AUCs). Approximately 60% of apafant is bound to plasma protein, the mean volume of distribution is 28 l, about 44% of an oral dose is excreted in the urine, the mean renal clearance is 192 ml/min. No accumulation of the drug occurred in volunteers with normal kidney function. No clinically relevant drug related adverse events or changes in laboratory or vital parameters such as blood pressure, heart rate, respiratory rate and ECG were observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1997

Anaphylactic bronchoconstriction in immunized guinea pigs provoked by inhalation and intravenous administration of hexahydrophthalic anhydride and methyltetrahydrophthalic anhydride.

We established a guinea-pig model of anaphylactic bronchoconstriction provoked in immunized animals by inhalation and intravenous administration of 4,4-methyltetrahydrophthalic anhydride (MTHPA) and hexahydrophthalic anhydride (HHPA). Guinea pigs were immunized intradermally with either MTHPA (n = 8) or HHPA (n = 8) suspended in olive oil. Control animals (n = 8) were injected with olive oil alone. After 4 weeks, the animals were challenged during mechanical ventilation by inhalation or intravenous administration of MTHPA or HHPA conjugated with guinea-pig serum albumin (GPSA). Airway flow, and airway and esophageal pressures were measured. Resistance (R) and static compliance (Cst) of the respiratory system (rs), lung (1), and chest wall were studied with the flow-interruption technique. After challenge with MTHPA-GPSA or HHPA-GPSA, R,rs and R,1 increased dramatically while Cst,rs and Cst,1 decreased, and severe arterial hypoxia developed. The reaction occurred at a well-defined dose of anhydride and lasted about 30 min. When the same dose was repeated after 30 min, the response was much attenuated. MTHPA and HHPA can induce asthma in guinea pigs. The dose-response curve at antigen challenge is steep. Once a threshold dose is reached, a severe reaction occurs. The reactivity is then exhausted. This model may be suitable for assessing occupational asthma caused by acid anhydrides and possibly by other low-molecular-weight chemicals.

Administration, Inhalation↗
PubMed2001

Pharmacokinetics of budesonide and its major ester metabolite after inhalation and intravenous administration of budesonide in the rat.

Fatty acid esterification of budesonide (BUD) has previously been documented in vitro as well as in large airway tissues after in vivo administration. This reversible esterification has the potential to prolong the anti-inflammatory effect of BUD and improve its airway selectivity. In the present study we characterized the plasma and tissue kinetics of BUD in the rat after inhalation and intravenous administration, and fitted a semiphysiological compartment model to the data. After inhalation, BUD half-life was longer (8.2 h) in trachea than in plasma (3.7 h), with similar data after intravenous dosing. BUD-oleate was formed in all tissues and had a longer half-life than BUD in trachea (18-20 h) but a similar half-life in plasma and muscle. Although the major fraction of BUD and BUD-oleate in the body was found in muscle, the airways, especially trachea, possessed a high capacity to form BUD-oleate. According to steady-state simulations, BUD-oleate accumulated in trachea, giving rise to persistent and higher concentrations of active BUD as compared with a situation wherein esters were not formed. BUD esters had no effect on plasma levels of BUD at steady state, however. BUD and BUD-oleate were shown to have a 2-fold and 10- to 50-fold selectivity, respectively, in airways as compared with muscle tissue after intravenous administration. After inhalation, the corresponding figures for selectivity were 10 and 50 to 1000, respectively.

Administration, Inhalation↗
PubMed1996

Glucocorticoid resistant asthma: T-lymphocyte steroid metabolism and sensitivity to glucocorticoids and immunosuppressive agents.

We have previously shown that T-lymphocytes from clinically glucocorticoid (GC) resistant asthmatics are more refractory to dexamethasone suppression in vitro than those of GC sensitive asthmatics. We wished to extend these observations to compare three GCs used topically for asthma therapy (budesonide, beclomethasone dipropionate and fluticasone 17 alpha-propionate) and three immunosuppressive drugs (cyclosporin A, FK506 (tacrolimus) and mycophenolate mofetil) with dexamethasone for their antiproliferative effects on T-lymphocytes from GC sensitive and resistant asthmatics, and also to compare the rates of steroid metabolism by T-lymphocytes from these patients. Antiproliferative activity of the drugs was measured on peripheral blood T-lymphocytes activated with phytohaemagglutinin (PHA) and anti-CD3 antibody in vitro. The rates of total steroid metabolism and 20 alpha-hydroxylation by T-cell homogenates were measured using radiolabelled progesterone as an established probe substrate. Over a wide concentration range, T-lymphocytes from GC resistant asthmatics were significantly less inhibited by all four GCs as compared with cells from GC sensitive asthmatics. The median inhibitory concentrations (IC50) for inhibition of T-lymphocytes from the GC resistant asthmatics exceeded those likely to be achieved therapeutically by systemic administration (although higher concentrations might in theory be achieved locally in the bronchial mucosa by inhaled administration). In contrast, all three immunosuppressive drugs at putative therapeutic concentrations inhibited T-lymphocytes both from GC sensitive and resistant asthmatics with equivalent potency. The rates of total metabolism and 20 alpha-hydroxylation of steroid by homogenates of T-lymphocytes from GC sensitive and resistant asthmatics were equivalent. Thus, relative GC resistance in T-lymphocytes from GC resistant as compared with sensitive asthmatics is: 1) manifest with GC molecules of variable molecular structure; 2) not accompanied by elevated intracellular metabolism of steroids; and 3) overcome by immunosuppressive drugs which inhibit T-lymphocytes by non-GC-mediated mechanisms. We conclude that current anti-asthma glucocorticoids at therapeutic concentrations are unlikely to be of benefit for the therapy of glucocorticoid resistant asthma, and that other immunosuppressive drugs may have potential as therapeutic agents in these patients.

Administration, Topical↗
PubMed1986

Optimal dose of fenoterol by metered-dose inhaler in asthmatic adults.

Three doses of fenoterol were administered by metered-dose inhaler to 20 adult subjects with asthma in order to determine the optimal dose for routine administration. Inhaled doses of 100 micrograms, 200 micrograms, and 400 micrograms of fenoterol with isoproterenol and placebo controls were administered in a randomized double-blind crossover regimen. We found that 200 micrograms of fenoterol by metered-dose inhaler produced a longer duration of action, greater peak response, and greater overall time-weighted responses in the forced expiratory volume in one second, in the mean forced expiratory flow during the middle half of the forced vital capacity, and in airway resistance than did the other drug regimens. The 400 micrograms dose of fenoterol produced no increase in response over that seen after the 200 micrograms dose. Side effects were minimal and no greater than with isoproterenol.

Administration, Intranasal↗
PubMed1991

Plasma levels and effects of salbutamol after inhaled or i.v. administration in stable asthma.

The response and plasma levels of inhaled (0.15 mg.kg-1) and intravenous salbutamol (5 micrograms.kg-1) were studied in 12 patients who had previously been included in a study of acute severe asthma and were now in a stable phase. The maximal value for change (delta) in plasma salbutamol compared with the pretreatment value was higher after i.v. than after inhalation treatment (59 vs 30 nmol.l-1) but the areas under the curve (AUC) during 90 mins after treatment were similar for the two administration routes. The inter-individual differences in peak plasma salbutamol and AUC for delta plasma salbutamol were much greater after inhalation than after i.v. infusion. Immediately after treatment there was a greater increase in pulse rate (mean +17 vs +6 beats.min) and lower serum potassium level (mean -0.3 mmol.l-1) after i.v. than after inhalation treatment. The increase in peak expiratory flow (PEF) measured 90 min after the start of treatment (85 vs 31 l.min-1) and as AUC was significantly higher after inhalation than after i.v. treatment. Six patients had received i.v. treatment in the acute asthma study: in these patients delta PEF immediately after i.v. treatment was significantly lower in the stable situation (+49 vs +115 l.min-1). There was also a significant difference in the effect on the pulse rate immediately after i.v. treatment, with a decrease in the acute asthma and an increase in the stable asthma situation (-5 vs +16 beats.min-1).

Administration, Inhalation↗
PubMed1982

Salbutamol in the treatment of asthmatic children. A comparison of oral and inhalation therapy alone and in combination.

In 10 children with asthma and reversible bronchial obstruction the effect on lung function (VC, FVC and FEV1) of salbutamol was tested comparing oral administration, inhalation or a combination of both. The oral treatment was carried out as a randomized double-blind salbutamol-placebo cross-over study followed by inhalation of salbutamol in all patients. In agreement with previous findings in adults, the study showed a significant increase of FEV1, FVC and VC (P less than 0.005) after oral salbutamol. Combined oral and inhalation medication of salbutamol gave a significantly higher increase of FEV1, VC (P less than 0.01) and FVC (P less than 0.05) when compared with oral therapy only. Compared with salbutamol inhalation only, the combined therapy gave a significantly higher FEV1 (P less than 0.01). The relatively high oral dose used produced no side effects.

Administration, Oral↗
PubMed2006

Mast cell mediator tryptase levels after inhalation or intravenous administration of high doses pharmaceutically prepared heroin.

BACKGROUND: Opioids like morphine and heroin induce mast cell degranulation in vitro. The release of mast cell mediators like histamine and tryptase may lead to allergic symptoms. In this study it was investigated whether mast cell mediator release also occurs in vivo in addicted patients who participated in a heroin on medical prescription trial, and were under treatment with large doses of heroin in combination with methadone. METHOD: Plasma levels of tryptase, a specific marker for mast cell degranulation, were measured by immuno-assay at baseline and 60 min after heroin administration. Heroin was administered either by intravenous injection (11 subjects) or by inhalation (nine subjects). Single heroin doses varied from 200 to 450 mg. Besides tryptase, the plasma concentrations of heroin, its metabolite morphine and methadone were measured. RESULTS: After heroin injection, the mean tryptase plasma concentration increased dose dependently by on average 23.1% (95% CI 14.6-31.6%). After heroin inhalation, no tryptase release was observed. Heroin and morphine peak plasma concentrations were 3-5 times greater in heroin injectors than in inhalers. In heroin injectors, tryptase levels were related to morphine peak concentrations, but not to heroin concentrations. Tryptase plasma concentrations were not related to methadone levels. Mild allergic reactions were reported in five cases after intravenous heroin use, but not after inhalation. CONCLUSION: This study revealed that mast cell mediator tryptase concentrations increase after intravenous heroin injection in chronic opioid users, but not after heroin inhalation. This may be explained by the higher Cmax levels of metabolite morphine that were achieved after injection than after inhalation. Although statistical significance was reached, the degree of mast cell degranulation after intravenous injection of heroin was mild, and did not lead to clinically relevant side effects in this group of opioid-tolerant subjects.

Administration, Inhalation↗
PubMed1989

Formoterol fumarate, a new beta 2-adrenoceptor agonist. Acute studies of selectivity and duration of effect after inhaled and oral administration.

Four double-blind, double-dummy, randomized, crossover studies were performed in nine asthmatic patients to evaluate beta 2-adrenoceptor selectivity and the duration of effect of formoterol. One study with cumulatively increasing doses of formoterol and salbutamol showed that with the inhaled route, formoterol was 5-15 times more potent than salbutamol with respect to bronchodilation. In a second study, 6 micrograms formoterol and 0.1 mg salbutamol were given for comparison of effect duration. Five hours after salbutamol inhalation the FEV1 values were back to basal. Eight hours after formoterol inhalation about 75% of the maximum bronchodilation remained and the FEV1 was significantly higher than after salbutamol inhalation. By oral route, a study with cumulatively increasing doses showed that as a bronchodilator formoterol was about 50 times more potent than salbutamol. The same potency difference was seen for increase of heart rate and decrease of diastolic blood pressure, indicating that the clinical selectivity for beta 2-adrenoceptors is equal for the two drugs. In a fourth study comparable doses by oral route did not show any difference in the duration of bronchodilation. We conclude that inhaled formoterol is 5-15 times more potent than salbutamol. Inhaled formoterol produces longer duration of bronchodilation, with clinically relevant bronchodilation for at least 8 h. The prolonged duration of formoterol was not seen with oral treatment.

Administration, Inhalation↗
PubMed1987

Chromosomal abnormalities and sister-chromatid exchange in bone marrow cells of mice and Chinese hamsters after inhalation and intraperitoneal administration: I. Diepoxybutane.

Diepoxybutane (DEB), a direct-acting animal carcinogen, was found to increase the frequency of structural chromosomal abnormalities (CA) and sister-chromatid exchange (SCE) in bone marrow cells of mice and Chinese hamsters, when inhaled from an aerosol during a 2-h head-only exposure or administered as a single intraperitoneal injection. For the purpose of comparing the genotoxicity in the 2 species, both after inhalation and intraperitoneal administration, the systemic DEB dose obtained by inhalation was determined on the basis of blood concentrations and inhalation duration after the investigation of the blood kinetics. The bone marrow cells of male and female NMRI mice were found to be more sensitive than those of Chinese hamsters to the genotoxic activity of DEB.

Administration, Inhalation↗