Nedocromil Research Articles

Use of prophylactic medication in persistent asthma

OBJECTIVE: To assess the proportion of patients with moderate or severe persistent asthma who are on prophylactic therapy when first evaluated at a specialized outpatient center. METHODS: Descriptive study of 306 patients with persistent asthma and ages ranging from four to fifteen years old, seen from June/1995 to August/1998, at the Respiratory and Allergic Diseases section of the Child and Adolescent Institute, an outpatient reference center located in the town of Juiz de Fora (MG), Brazil. Data from the Institute's registry, chiefly those related to the use of prophylactic medications, such as inhaled steroids, sodium chromoglycate, nedocromil sodium, sustained-release theophylline, long acting inhaled beta2-agonist and ketotifen were used to fill in a standardized protocol. RESULTS: Of the 306 patients, 87.3% had persistent moderate and 12.7% had persistent severe asthma. Only 14.4% were on some kind of controller medication. When only the use of inhaled antiinflammatory drugs (sodium cromolyn, nedocromil sodium and steroids) was considered, this proportion decreased to 4.6%. There was not statistical significance (p<0.05) between the use or not of prophylactic regimens in relation to gender, weight, height, asthma severity, hospital admissions, age of onset, age when first evaluated at the outpatient center and household smoking. CONCLUSIONS: The rate of utilization of prophylactic regimens in this population of persistent asthmatic patients was unsatisfactory, a finding particularly stressed by the low rate of subjects on inhaled antiinflammatory drugs. It is necessary to emphasize such measures to face the magnitude that asthma represents in our country.

Comparison of topical nedocromil sodium and oral terfenadine for the treatment of seasonal allergic conjunctivitis

This double-masked, comparative, multicenter study was conducted to assess the onset of action and tolerability of nedocromil sodium 2% ophthalmic solution BID, 60-mg terfenadine tablets BID, and placebo in the treatment of seasonal allergic conjunctivitis. Two hundred sixty-eight patients in whom seasonal allergic conjunctivitis was diagnosed were assigned to 1 of 3 groups and administered study medication for 4 weeks. Patients' mean age was 33 years (range, 12 to 68 years); 57.8% (155 of 268) were female. Demographic characteristics were similar in all 3 groups. Although all 3 groups showed improvement in ocular symptoms, nedocromil sodium was associated with a statistically significantly faster onset of action than was terfenadine or placebo ( P = 0.038). During the study, 29 nedocromil sodium-treated patients (36.7%) achieved control of symptoms in <-2 minutes, and 61 (77.2%) achieved control in <-15 minutes. The corresponding numbers were 21 (24.7%) and 50 (58.8%) in the terfenadine group and 25 (29.1%) and 48 (55.8%) in the placebo group. The frequency of adverse events was low and similar between groups (nedocromil sodium, 26; terfenadine, 32; placebo, 32). No severe treatment-related adverse events were reported. In conclusion, nedocromil sodium had a significantly faster onset of action than did terfenadine or placebo.

Sputum eosinophil count to assess compliance with corticosteroid therapy in asthma

Sputum eosinophil count to assess compliance with corticosteroid therapy in asthma

Modulation of HLA-DR antigen and ICAM-1 molecule expression on airway epithelial cells by sodium nedocromil.

To test in vitro and in vivo the hypothesis that sodium nedocromil could modulate the expression of surface molecules on airway epithelial cells. Human bronchial epithelial cells, obtained from surgically resected bronchi, were cultured and stimulated with recombinant IFN-gamma in the presence of sodium nedocromil. The intensity of the expression of surface molecules HLA-DR and ICAM-1 molecules on bronchial epithelial cells in vitro, was quantified by specific antibody staining and flow-cytometry analysis. Furthermore, we studied the effect of the drug on airway inflammation in vivo and on allergic rhinitis patients sensitized to house dust mites. Nasal epithelial cells were collected by brushing, at baseline and 2 to 3 weeks after treatment with sodium nedocromil. The expression of HLA-DR and ICAM-1 molecules was measured by flow-cytometry, and the proportions of neutrophils and eosinophils "contaminating" the epithelial cells evaluated by light microscopy examination of nasal brushings. The enhanced HLA-DR and ICAM-1 expression, induced by IFN-gamma, was effectively downregulated, in a dose-dependent manner, by sodium nedocromil. At all the concentrations tested (10(-9) to 10(-4) M), the inhibitory activity of the drug was stronger on HLA-DR than on ICAM-1 expression (P<.05, all comparisons). As compared with healthy subjects, patients with allergic rhinitis had a higher expression of HLA-DR (P<.05) but not of ICAM-1 molecules (P>.05) on nasal epithelial cells, and higher proportions of nasal eosinophils (P<.05). Treatment with sodium nedocromil downregulated the expression of HLA-DR (P<.05), but not of ICAM-1 (P>.05), and induced a mild, but not statistically significant, decrease of nasal eosinophilia (P>.05). These data demonstrate that the antiinflammatory activity of sodium nedocromil may include modulation of surface molecule expression on airway epithelial cells.

Regular albuterol or nedocromil sodium — effects on airway subepithelial tenascin in asthma

Both albuterol and nedocromil sodium have been recognized to possess certain anti-inflammatory properties. However, there are no data on the impact of these drugs on the pathophysiology of the bronchial extracellular matrix in asthma characterized by enhanced tenascin (Tn) expression, known to occur proportional to the severity of asthma. This paper reports data from a morphometric study on the effects of regular treatment with inhaled albuterol or nedocromil sodium on the extent of bronchial subepithelial deposition of Tn, collagen types III, IV, and VII and mucosal infiltration with macrophages. Thirty-two patients (14 women) with chronic asthma, aged 38·7 years (median) with a median forced expiratory volume in 1 sec (FEV 1) of 74·4% predicted, were selected to undergo fibre-optic bronchoscopy with bronchial biopsies before and after 12 weeks of treatment with either inhaled albuterol 0·2 mg or nedocromil sodium 4 mg four times daily according to a double-blind protocol. Cryostat sections of the biopsy specimens were studied by indirect immunostaining techniques using monoclonal antibodies and computer-assisted quantitative image analysis. Albuterol treatment significantly reduced the median thickness of subepithelial Tn expression from 9·7 to 6·3 μm ( P=0·023) and macrophage numbers in the epithelium ( P=0·034), lamina propria ( P=0·039) and entire mucosa ( P=0·033), whereas nedocromil sodium had no effect. Expression of the collagen types was not affected by either treatment. There was no identifiable statistical difference between the two treatments for any of the outcome variables measured. Nevertheless, the results demonstrate that even a short-acting β 2-agonist may exert anti-inflammatory potential sufficient to interfere with the basic mechanisms of asthma as shown by reduction of subepithelial Tn content and mucosal macrophage count.

Comparative Effects of Betamethasone, Cyclosporin and Nedocromil Sodium in Acute Pulmonary Inflammation and Metalloproteinase Activities in Bronchoalveolar Lavage Fluid from Mice Exposed to Lipopolysaccharide

Matrix metalloproteinases (MMPs) are particularly potent in degrading basement membrane collagen associated with lung injury in inflammatory processes. We have investigated the effects of betamethasone, cyclosporin, and nedocromil on MMP2 and MMP9 activities, on TNF-α and IL-10 release, as well as on the recruitment of inflammatory cells in the bronchoalveolar lavage (BAL) fluid after aerosol administration of lipopolysaccharide (LPS) in mice. When mice were pretreated with betamethasone (5 mg/kg, po), MMP2 and MMP9 activities, TNF-α in BAL fluids, and the enhanced neutrophil number of LPS-exposed mice were reduced, whereas the level of IL-10 was increased. Pretreatment of mice with cyclosporin (10 mg/kg, po) did not significantly reduce MMP activities, but cyclosporin inhibited neutrophil recruitment, inhibited increase TNF-αand inhibited IL-10 decrease. Nedocromil sodium (30 mg/kg, ip) had no influence on the LPS-induced MMP activities, on neutrophil recruitment, or on IL-10 level, but this drug elicited a significant inhibition of TNF-αlevel. These results showed that treatment with the antiinflammatory drugs cyclosporin and nedocromil sodium did not lead to reduction of MMP release. However, since betamethasone reduced the LPS-induced pulmonary inflammation and production of MMPs, these results suggest that corticosteroids may decrease tissue remodelling associated with acute lung injury.

Effect of nedocromil sodium on non-adrenergic, non-cholinergic neural responses in guinea pig bronchi in vitro

Objective: Nedocromil sodium (nedocromil) improves the clinical condition of asthmatic subjects but its mechanism of action is not fully understood. This study aimed to determine whether nedocromil alters the ability of contractile and relaxant non-adrenergic, non-cholinergic neural (NANC) responses to stabilise tone by inhibiting or potentiating these responses in bronchial smooth muscle and, if so, whether the action is on a pre- or postjunctional level. Results: Nedocromil attenuated contractile but not relaxant NANC responses (elicited by electric field stimulation) significantly ( P<0.05) in guinea pig main bronchi in vitro. However, the ability of NANC responses to stabilise tone (convergence effect) was not significantly impaired by nedocromil. Furthermore, nedocromil did not significantly shift the concentration response curve (−log EC 50) to neurokinin A (NKA), the dominating contractile NANC transmitter, or alter the maximum response to NKA ( P>0.05). Submaximum or maximum contractile responses to histamine were not markedly affected by nedocromil ( P>0.05). Conclusions: Nedocromil exerts selective neural inhibition of the contractile but not of the relaxant NANC responses on a pre-junctional level in bronchial smooth muscle. Nedocromil does not, however, markedly impair the ability of NANC response to stabilise bronchial smooth muscle tone.

Early use of inhaled nedocromil sodium in children following an acute episode of asthma

BACKGROUNDCurrent guidelines on the treatment of childhood asthma recommend the introduction of an anti-inflammatory drug in children who have persistent symptoms and require regular treatment with a bronchodilator. The efficacy...

In-vitro Evaluation of Dry Powder Inhaler Formulations of Micronized and Milled Nedocromil Sodium

The aerosol properties of dry powder inhaler formulations of micronized and milled nedocromil sodium were investigated. Milled and micronized drug, alone or with a carrier (α-lactose monohydrate) were filled into hard gelatin capsules. These were placed into a proprietary dry powder inhaler device, the Rotahaler. The powders were liberated into a twin impinger operated at 60L min−1, and the drug deposited within the impinger and remaining in the device, was assayed. The results indicate that the α-lactose monohydrate carrier was necessary for optimal liberation of nedocromil sodium from the device and deposition in the lower stage of the impinger. Micronized drug (median size = 1.6 μm) was less efficiently delivered to the lower stage than milled drug (median size = 7-2 μm). Size reduction of nedocromil sodium, by micronization, to produce particles of optimal size for deep lung penetration, may alter the properties of the particles, such that they are more cohesive and adhesive and may consequently be delivered less effectively as dry powder aerosols than larger particles.

A randomised trial of the initiation of asthma treatment

Objective:To compare the effectiveness of four classes of anti-asthma medication as initial treatment in a randomised open study in an asthma clinic setting.Design and subjects:Eighty-six patients aged 16–70 years were recruited into an open trial following informed consent. The diagnosis of asthma was established by either a 15% diurnal variability in peak expiratory flow (PEF) or a > 15% bronchodilation to inhaled salbutamol. Patients were randomised to one of the following drug classes: a short-acting β2-agonist (n = 21); an inhaled steroid (n = 25); nedocromil sodium 4mg qds (n = 22); and oral theophylline (n = 18). Symptoms and daily PEF measurements were recorded on a diary record card.Results:Baseline characteristics of the four groups were similar. Mean FEV1 (predicted) and FVC were 2.61 (82%) and 3.61 (91%), respectively. Wheeze, cough and expectoration were present on 4.2, 3.8 and 2.8 days per week. At one month, the greatest improvement in number of symptom-free days was seen in the group taking the inhaled steroids. Mean days per week with wheeze fell by 1.3 (p < 0.05), cough by 0.5 (NS) and expectoration by 1.5 (p < 0.05). Nedocromil sodium produced a mean decrease in symptom days of 0.8, 0.3 and 0.8, respectively (NS). Other modalities of treatment produced no significant change in symptoms. Mean improvement in FEV1 was greatest in the steroid group (11%; p <0.02) followed by nedocromil sodium (9%; p < 0.02). There was no change with short-acting β2-agonists or theophylline.Conclusions:Initiation of treatment with anti-inflammatory therapy produces the greatest symptomatic and physiological improvement in mild asthma.

Efficacy of nedocromil 2% versus fluorometholone 0.1%: a randomised, double masked trial comparing the effects on severe vernal keratoconjunctivitis

AIMS To compare the efficacy of topical nedocromil 2% with fluorometholone 0.1% in vernal keratoconjunctivitis (VKC). METHODS In a double masked random design, 24 patients with severe vernal keratoconjunctivitis were...

Médicaments antiallergiques et pathologie respiratoire de l'enfant

Second generation antihistamines (anti H1) are effective for seasonal and perennial rhinoconjunctivitis curative or preventive treatment in children. They are better tolerated than first generation drugs. They probably do not act specifically against asthma itself, but are nevertheless useful for relief of nasal obstruction, which is an asthmogenic factor frequently linked with bronchial asthma. The therapeutic relevance of oral ketotifen and inhaled chromones (sodium cromoglycate, nedocromil sodium) is unequally considered among pediatricians. However, their efficacy has been clearly demonstrated as a ground treatment in mild-to-moderate asthmatic children. Chromones are also useful in preventing exercise-induced asthma. Because of their low cost and the lack of potential side effects, and according to the guidelines established in 1997 by the National Heart, Lung and Blood Institute, they should be prescribed at first sight in these indications.

Treating severe eye allergy.

Allergic eye conditions, particularly seasonal allergic conjunctivitis (SAC), are common. Itching, oedema and hyperaemia are relieved with topical H1-antagonists or sodium cromoglycate. The newer mast-cell stabilizing agent nedocromil sodium has a similar safety profile to sodium cromoglycate, but is more potent and has a more convenient twice-daily dosing regimen. When several placebo-controlled studies of its use in the treatment of SAC were analysed, it was found that 80% of patients reported symptom relief. In a further study, nedocromil sodium eyedrops (twice-daily dosing) had similar overall efficacy to sodium cromoglycate eyedrops (four-times-daily dosing) in subjects with SAC during the birch season, but during the period of highest pollen challenge, only the former agent was significantly more effective than placebo. Another study found that nedocromil sodium had efficacy equivalent to levocabastine over 7 days, but tended to have a more rapid onset of action. In patients with perennial allergic conjunctivitis (PAC) unresponsive to sodium cromoglycate, both clinicians and patients reported significantly better control of symptoms with nedocromil sodium eyedrops than with placebo. Recently, in a long-term study of treatment for vernal keratoconjunctivitis (VKC), it was found that nedocromil sodium 2% eyedrops produced a more rapid and marked improvement in symptoms than sodium cromoglycate 2% eyedrops and enabled lower use of steroid rescue medication. Both drugs were well tolerated and without serious side-effects.

Expression of ICAM-1 and HLA-DR by Human Conjunctival Epithelial Cultured Cells and Modulation by Nedocromil Sodium

It is unclear whether conjunctival epithelial cells participate in the development of immune-mediated events. Using a previously reported in vitro system of human conjunctival epithelium, we determined whether conjunctival epithelial cells express two relevant markers in the antigenic presentation process. Moreover, the potential capability of nedocromil sodium, an antiallergic and antiinflammatory drug, to modulate such expression was investigated. Primary cultures of human conjunctival epithelium and Chang conjunctival cells, incubated with or without 100 U/ml IL-1beta and/or IFNgamma for 1, 3 or 6 h, were simultaneously exposed to 10(-5) M nedocromil sodium. The expression of the intercellular adhesion molecule-1 (ICAM-1) and the human leukocyte antigen-DR (HLA-DR) was determined immunocytochemically. Constitutive expression of ICAM-1 and HLA-DR was observed in primary cultures and Chang cells and was minimally affected by incubation with IL-1beta and/or IFNgamma. The addition of nedocromil sodium resulted in complete abolition of HLA-DR expression and a notable reduction in ICAM-1 expression in primary cultures and Chang cells. These results suggest that epithelial cells from human conjunctiva constitutively express ICAM-1 and HLA-DR in vitro and that such expression is downregulated by nedocromil sodium. This may indicate that conjunctival epithelial cells may be another target for this drug.

Poly( l-lactic acid) microspheres for pulmonary drug delivery: release kinetics and aerosolization studies

We have previously developed poly( l-lactic acid) (PLA) microspheres containing nedocromil sodium and beclomethasone dipropionate (BDP) for aerosolisation to the respiratory tract (El-Baseir, M.M., Phipps, M.A., Kellaway, I.W., Preparation and subsequent degradation of poly( l-lactic acid) microspheres suitable for aerosolisation: a physico-chemical study. Int. J. Pharm. 151 (1997) 145–153). In this study we have investigated the in vitro release kinetics of these two drugs from PLA microspheres and the deposition of the microspheres in an in vitro lung model (Andersen cascade impactor) following aerosolisation from a dry powder inhaler (Spinhaler ®). The in vitro kinetics of drug release revealed a controlled release of nedocromil sodium over 8 days with a burst effect (27–60%, w/w) which varied with the particle size of the microspheres. For BDP entrapped in PLA microspheres, controlled release of BDP occurred over 6 days. BDP release was determined by measuring the shift in the phase transition temperature of dimyristoylphosphatidylcholine (DMPC) liposomes induced by partitioning of the steroid into the lipid bilayers. The residual poly(vinyl alcohol) used as an emulsifier in the production of the microspheres was < 7% (w/w). The in vitro deposition of the microspheres (1.00 ± 0.21 μm) containing BDP from a Spinhaler ® to a cascade impactor at a flow rate of 60 l/min, resulted in 20% of the emitted dose deposited on stages corresponding to particles < 3 μm and approximately 42% < 5 μm.

Insensitivity of volume-sensitive chloride currents to chromones in human airway epithelial cells.

Chromones (sodium cromoglycate and sodium nedocromil) block cell swelling-activated Cl- channels in NIH-3T3 fibroblasts and endothelial cells. This has led to hypothesize that cell volume regulation might be involved in asthma pathogenesis. Using whole-cell patch-clamp experiments, we studied the effect of chromones on volume-sensitive Cl- currents in transformed human tracheal epithelial cells (9HTEo-) and in primary cultures of human bronchial epithelial cells (BE). Cl- currents activated by hypotonic shock were poorly blocked by extracellular nedocromil or cromoglycate. The block was voltage-dependent since it was observed only at positive membrane potentials. At the concentration of 5 mM, the current inhibition by both chromones at +80 mV was about 40% for 9HTEo- and only 20% for BE. Intracellular application of chromones elicited a voltage-independent inhibition in 9HTEo- cells. Under this condition, volume-sensitive Cl- currents were reduced at all membrane potentials (60 and 45% inhibition by 2 mM nedocromil and cromoglycate respectively). In contrast intracellular chromones were ineffective in BE cells. The relative refractoriness to chromones, in contrast with the high sensitivity shown by other Cl- channels, suggests that the epithelial volume-sensitive Cl- channel is not involved in asthma.

Validation of a high-performance liquid chromatography assay for urinary nedocromil sodium following oral and inhaled administration

The validation of a solid-phase extraction and an ion pair high-performance liquid chromatographic assay for the determination of nedocromil sodium (NCS) in urine samples following oral and inhaled administration to healthy volunteers is described. NCS and its internal standard sodium cromoglycate (SCG) were extracted from urine samples using solid-phase extraction and then quantified using high-performance liquid chromatography (HPLC). A 25-cm C 8 Spherisorb 5 μm stationary phase with a mobile phase containing a long alkyl chain ion-pair reagent (methanol–0.045 M phosphate buffer–0.05 M dodecyl triethyl ammonium phosphate; 550:447.6:2.4, v/v) was used. The mean (S.D.) intra-day accuracy and precision of the HPLC assay was 99.9 (1.6) and 7.05 (4.9)%, respectively. These values for the inter-day data were 102.4 (4.07) and 10.5 (2.7)%, respectively, over the concentration range investigated. The method described permits the detection of NCS in human urine at concentrations as low as 0.04 μg ml −1 where the signal-to-noise ratio is greater than 3:1. In 10 healthy volunteers a significantly greater amount of NCS was excreted in the urine following inhalation than after oral dosing ( p<0.001). The mean (S.D.) amount of NCS renally excreted at 0.5, 1.0 and 24 h following inhalation of four 2-mg doses of NCS from a metered dose inhaler (MDI) was 0.513 (0.24), 1.163 (0.49) and 4.00 (1.73)% of the nominal dose. Similar values after oral administration of 8 mg of NCS were 0.026 (0.03), 0.079 (0.06) and 0.930 (0.74)%, respectively.

Physical characterization of nedocromil sodium hydrates

Nedocromil sodium, which is used in the treatment of reversible obstructive airway diseases, such as asthma, is found to exist in the following hydrate phases: the heptahemihydrate, the trihydrate, a monohydrate, and an amorphous phase which contains variable amounts of water (1.5−3.0 mol). An anhydrate phase is formed from the trihydrate at zero humidity at ≥ 150°C, but is rapidly hydrated under ambient conditions. The physical and thermodynamic properties of the four hydrate phases were characterized using differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), powder X‐ray diffraction (PXRD) at ambient and elevated temperatures, hot‐stage microscopy (HSM), solid phase interconversion at various relative humidities (RH), intrinsic dissolution rate (IDR), equilibrium solubility measurements, and critical RH measurements. Below 100°C in open pan TGA, the heptahemihydrate and the amorphous forms lose virtually all their water, the monohydrate loses negligible amounts of water, whereas the trihydrate loses the first two moles of water. From 130°C to 200°C in open pan TGA the trihydrate and the monohydrate lose their last mole of water to form the anhydrate. In crimped pan DSC, the thermal events observed are analogous to those observed in open pan TGA, but the temperatures are increased by about 75°C for all except the heptahemihydrate, for which the thermal events are more complex. When the heptahemihydrate is heated in a crimped pan, a melting endotherm is observed at about 75°C followed by three dehydration endotherms. For the crystalline hydrate phases at 22°C, the ranges of stability are as follows: the monohydrate from 0 to 6.4% RH; the trihydrate from 6.4 to 79.5% RH; the heptahemihydrate above 80% RH. A microbalance study showed that the heptahemihydrate is kinetically stable over the range 11 to 79.5% RH. The IDR in water at 25°C under constant hydrodynamic conditions decreases in the rank order: monohydrate > trihydrate > heptahemihydrate, corresponding to the rank order of free energy with respect to the aqueous solution. The equilibrium aqueous solubility of the heptahemihydrate at 25.0 ±0.2°C is 0.956 ±0.010 M.

Effect of Nedocromil Sodium on Leukotrienes and Platelet-Activating Factor Release in Asthmatic Children

Airway inflammation is the most important component of asthma. Leukotrienes (LTB4, LTB-C4, LTB-D4, LTB-E4) and platelet-activating factor (PAF) play an important role in this inflammation. The pulmonary and peripheral leukocytes of asthmatics have a high potency of mediator-releasing activity after specific stimuli, and plasma levels of these are higher than in healthy controls. Nedocromil sodium (NES) is an inhaled anti-inflammatory drug and its inhibitory effect on inflammatory or epithelial cells has been demonstrated. The aim of this study was to determine whether inhaled NES affects plasma levels and release of PAF and leukotrienes from peripheral leukocytes of asthmatic children that were stimulated by house dust mites (as a specific allergen). Twenty-eight children (9 to 15 years of age) with atopic bronchial asthma were included in the study. They consisted of two age- and sex-matched groups (14 patients in the treatment group [group I]; 14 patients in the control group [group II]). Group I patients received inhaled NES (12 mg/d) for 12 weeks. Blood samples were drawn in the pre- and post-treatment periods. The measurements of plasma levels and secreted mediators levels after stimulation by house dust mites were performed with highpressure liquid chromatography (HPLC) and radioimmunoassay (RIA) methods. There were no significant differences between pretreatment plasma levels and secreted leukotrienes and PAF values of both groups. At the end of the study, significant decreases in plasma and in vitro stimulated LTB4, LT-C4, LT-D4, LT-E4, and PAF levels in group I were observed. There were no changes in the group II values. These in vivo and in vitro results suggest that NES is an effective anti-inflammatory drug for controlling childhood asthma by decreasing the high levels of inflammatory mediator release and immune cell activation.

Extension of Clausius-Clapeyron Equation to Predict Hydrate Stability at Different Temperatures

ABSTRACTThe objectives of this study were to verify theoretically and experimentally that the Clausius-clapeyron equation can be applied to a hydrate system, and to use this equation to predict the equilibrium water activity for a hydrate pair existing in equilibrium at different temperatures for the determination of the ranges of hydrate stability. The Clausius-Clapeyron equation was derived for hydrate systems by assuming (a) the higher and the lower hydrates exist in equilibrium with water vapor as three pure phases; and (b) the overall volume change involved in this equilibrium process is approximated by the volume of the released water vapor, which behaves ideally. The equilibrium water vapor pressure at different temperatures for the nedocromil sodium monohydrate and trihydrate system was determined dynamically using a thermogravimetric analyzer with an attached water vapor delivery system. The enthalpy of dehydration obtained by applying the Clausius-Clapeyron equation to the experimentally determined equilibrium water vapor pressures is in fair agreement with the enthalpy of dehydration derived from di'erential scanning calorimetry (13.7 ± 0.6 kcal/mol of water loss, n = 5), indicating that the Clausius-Clapeyron equation can indeed be applied to organic hydrate systems. The application of the Clausius-Clapeyron equation to predict the hydrate stability under various conditions is also discussed.