THE ACTIVITY OF SODIUM CROMOGLYCATE ANALOGUES IN HUMAN LUNG <i>in vitro</i>: A COMPARISON WITH RAT PASSIVE CUTANEOUS ANAPHYLAXIS AND CLINICAL EFFICACY

Church, Martin K.; Gradidge, Carolyn F.

doi:10.1111/j.1476-5381.1980.tb07937.x

Cited by 32 publications

(21 citation statements)

References 20 publications

(9 reference statements)

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“…Following 19 h pre-incubation with 200 fuM sodium cromoglycate, the effects produced by acute addition (Sheard 1978;Sharpe et al, 1978;Butchers et al, 1979;Church & Gradidge, 1980b;Young & Church, 1983). This observation also verifies that sodium cromoglycate is less effective in inhibiting degranulation of human mast cells than it is of rat mast cells (Thomson & Evans, 1973;Orr, 1977 , 1976).…”

Section: Cross-tolerance Between Sodium Cromoglycate and Other Drugsmentioning

confidence: 83%

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The characteristics of inhibition of histamine release from human lung fragments by sodium cromoglycate, salbutamol and chlorpromazine

Church

Young

1983

British J Pharmacology

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1 Three drugs have been tested for activity against antigen-induced histamine release from passively sensitized human lung fragments after increasing periods of pre-incubation before challenge. 2 After 30 s pre-incubation, sodium cromoglycate inhibited histamine release in the concentration range 0.2-200 iM, producing a maximum inhibition of 33.0%. As the pretreatment period was extended, tolerance developed in a dose-related manner, resulting in a 48.3 % and 82.8% loss of activity of the 200 AM dose after 60 min and 19h pre-incubation, respectively. Tolerance was independent of extracellular calcium and was poorly reversible. Lung tissue desensitized to cromoglycate was cross-tolerant to the related drug, bufrolin, but not to salbutamol or chlorpromazine.3 In acute studies, salbutamol (0.03-3.0 lJM) produced dose-related inhibition of histamine release, with a maximum inhibition of 72.2%. The effect was blocked stereoselectively by 1 JAM propranolol, suggesting that it occurred through an interaction with lung 3-adrenoceptors. Increasing the pre-incubation time with salbutamol from 30 s to 19 h did not produce tolerance. Inhibition produced by incubation with salbutamol for 19 h was totally prevented when propranolol was added at the beginning of the pre-incubation period, indicating that it resulted from stimulation of P-receptors and not from a non-specific or toxic effect. However, studies of reversibility of effect through washing or late addition of propranolol did indicate some change in the nature of salbutamol inhibition with time. 4 Chlorpromazine was a weak inhibitor of immunological histamine release. A 100 ltMconcentration was ineffective after 30 s pre-incubation but its activity increased with time. Pre-incubation of lung fragments with this concentration for 1 h or longer, or with a 1 mM dose for a shorter period, provoked histamine release in the absence of antigen. Effects of chlorpromazine were not reversed by washing. 5 The different characteristics shown by sodium cromoglycate, salbutamol and chlorpromazine indicate that these drugs inhibit histamine release by interfering with the secretory mechanisms in different ways.

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Section: Cross-tolerance Between Sodium Cromoglycate and Other Drugsmentioning

confidence: 83%

“…Skidmore, Thomson, Vardey & Wheeldon, 1979; 6) The Macmillan Press Ltd 1983 Church & Gradidge, 1980b;Young & Church, 1982). With ,B-adrenoceptor stimulants, the situation is reversed.…”

Section: Introductionmentioning

confidence: 99%

The characteristics of inhibition of histamine release from human lung fragments by sodium cromoglycate, salbutamol and chlorpromazine

Church

Young

1983

British J Pharmacology

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“…Other studies suggest that the acute effects of SCG in extrinsic asthma are due to its ability to stabilize mast cells independently of the stimulus applied and thus prevent the release of mediators (Cox, Beach, Blair, Clarke, King, Lee, Loveday, Moss, Orr, Ritchie & Sheard, 1970). Clinical trials with SCG have shown a strong carry-over effect after long-term treatment (Kennedy, 1969;Bernstein, Siegel, Brandon, Brown, Evans, Feinberg, Friedlaender, Krumholz, Hadely, Handelman, Thurson & Yamata, 1972 (Church & Gradidge, 1980) and other mechanisms of action have been considered. Histamine, one of the main mediators liberated at an antigen-antibody reaction in guineapigs, is thought to trigger a bronchoconstriction through an 'irritant' receptor, parasympathetic reflex mechanism (for references see Boushey, Holtzman, Sheller & Nadel, 1980).…”

Section: Discussionmentioning

confidence: 99%

Antigen‐induced Bronchial Anaphylaxis in Actively Sensitized Guinea‐pigs: Effect of Long‐term Treatment With Sodium Cromoglycate and Aminophylline

Andersson

Bergstrand

1981

British J Pharmacology

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The effects of long‐term treatment with sodium cromoglycate (SCG) and aminophylline on antigen‐induced bronchoconstriction have been studied in guinea‐pigs actively sensitized according to two different regimens (one producing IgE‐ and IgG‐like antibodies and the other producing exclusively IgG‐like antibodies). Treatment for three weeks with SCG (10 mg/kg) and aminophylline (10,30 or 60 mg/kg) led to a decreased bronchial response capacity which persisted even three days after treatment ceased. In this respect SCG was effective only in guinea‐pigs sensitized to produce at least partly IgE‐like antibodies; aminophylline was effective in guinea‐pigs sensitized to produce both IgE and/or IgG antibodies. The results in vivo with SCG were reflected in vitro by a reduced capacity of chopped lung tissue to release histamine at antigen challenge; lungs from animals treated with aminophylline did not show reduced histamine releasing capacity. Acute treatment with atropine was shown to reduce significantly the antigen‐induced bronchial contraction in guinea‐pigs sensitized to produce both IgE‐ and IgG‐antibodies. No effect of atropine was seen on an IgG‐mediated anaphylaxis. Increased reactivity to methacholine but not to histamine was seen in guinea‐pigs sensitized to produce both IgG‐ and IgE‐antibodies. Long‐term treatment with SCG did not affect this hyperreactivity to methacholine. Decreased reactivity to isoprenaline was found in isolated tracheae taken from guinea‐pigs sensitized to produce both IgE‐ and IgG‐like antibodies compared to unsensitized guinea‐pigs. Long‐term treatment with SCG, but not with aminophylline, reversed this decreased reactivity.

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“…However, not all asthmatics benefit from these drugs [6] and thus, there is a medical need for safe and effective agents to treat this condition. Figure 1) is a new antiallergic agent which has been selected for its in vitro and in vivo activity in experimental models of anaphylaxis and allergic conjunctivitis [7][8][9].…”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetics of andolast after administration of single escalating doses by inhalation in mild asthmatic patients

Persiani¹,

D’Amato²,

Makovec³

et al. 2001

Biopharm & Drug Disp

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The pharmacokinetics of andolast, a new tetrazolyl-benzamido derivative with antiallergic, antiinflammatory, mucosal protective and antisecretive activities, have been investigated in patients suffering from mild asthma (FEV(1) > or =70% of predicted) in whom obstruction was reversible (FEV(1) increase > or =15% of initial) after the administration of 0.2 mg of salbutamol by inhalation. Twelve out-patients (seven males and five females) were enrolled in the present study and were treated with a single dose of andolast of 2, 4 and 8 mg by inhalation using the MIAT Monohaler device according to a randomised crossover design. Plasma samples were collected before drug administration and up to 540 min after dosing. Andolast plasma concentrations were determined using a validated LC-MS/MS method with a limit of quantitation of 0.2 ng ml(-1). Pharmacokinetic analysis was carried out using standard non-compartmental methods. In addition, andolast safety and tolerability were evaluated by performing standard laboratory tests, by recording vital signs and ECGs and by monitoring the occurrence of adverse events throughout the study period. Andolast was absorbed after inhalation and was available to the systemic circulation. The mean peak plasma concentrations were 6.3, 10.9 and 30.5 ng ml(-1) at the three doses, respectively, and occurred at 30, 52.5 and 30 min (median t(max)). The mean AUC(t) values were 1852, 2889 and 7677 ng min ml(-1). The apparent plasma clearance (CL/F) and volume of distribution (V(z)/F) were, respectively, 1168 ml min(-1) and 430 l at the dose of 2 mg, 1143 ml min(-1) and 468 l at the dose of 4 mg, and 1141 ml min(-1) and 486 l at the dose of 8 mg. The apparent elimination half-life averaged 4.5, 5.0 and 4.6 h at the three doses, respectively. Even though the small number of subjects participating in the present study reduced the power of the statistical test, there was no statistically significant evidence of non-proportionality for all the andolast pharmacokinetic parameters calculated at the three doses. Thus, the data obtained as a whole suggest that andolast pharmacokinetics are dose-independent in the dose range investigated. Finally, the safety and tolerabilty of the drug administered to mild asthmatic patients was good up to the maximum investigated dose of 8 mg.

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THE ACTIVITY OF SODIUM CROMOGLYCATE ANALOGUES IN HUMAN LUNG in vitro: A COMPARISON WITH RAT PASSIVE CUTANEOUS ANAPHYLAXIS AND CLINICAL EFFICACY

Cited by 32 publications

References 20 publications

The characteristics of inhibition of histamine release from human lung fragments by sodium cromoglycate, salbutamol and chlorpromazine

The characteristics of inhibition of histamine release from human lung fragments by sodium cromoglycate, salbutamol and chlorpromazine

Antigen‐induced Bronchial Anaphylaxis in Actively Sensitized Guinea‐pigs: Effect of Long‐term Treatment With Sodium Cromoglycate and Aminophylline

Pharmacokinetics of andolast after administration of single escalating doses by inhalation in mild asthmatic patients

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