Targeting glycometabolic reprogramming to restore the sensitivity of leukemia drug-resistant K562/ADM cells to adriamycin.

AIMS: Mounting studies have confirmed that cancer cells reprogram their metabolism during early carcinogenesis to develop many other hallmarks, and demonstrated a relationship between aerobic glycolysis and the occurrence of drug resistance. However, the molecular mechanisms and role in tumor drug resistance of aerobic glycolysis remain unclear. MAIN METHODS: We analyzed differentially expressed genes (DEGs) at the RNA level between the multi-drug resistance (MDR) leukemia cell line K562/adriamycin (ADM) and its parental, drug-sensitive K562 cell line. Clustering and enrichment analysis of DEGs was performed. Oxamate, a lactic dehydrogenase inhibitor were used to assess the effect of glycolysis inhibition on ADM susceptibility and the expression of the enriched DEGs in K562/ADM cells. KEY FINDINGS: A total of 1742 DEGs were detected between the K562/ADM and K562 cell lines. The differential expression of unigenes encoding enzymes involved in glycometabolism signifies that there was a greater aerobic glycolysis flux in K562/ADM cells. The PI3K-AKT signaling pathway, which is related to glucose metabolism, showed representative differential enrichment and up-regulation in K562/ADM cells. Oxamate improved and re-sensitized the therapeutic effect of ADM in ADM-resistant cells by inhibiting aerobic glycolysis either directly or indirectly by down-regulation of the AKT-mTOR pathway. SIGNIFICANCE: Our findings suggest that ADM resistance mediated by the increase of aerobic glycolysis, which related to the over-activation of the AKT-mTOR-c-Myc pathway in MDR leukemia cells. Inhibition of aerobic glycolysis and down-regulation of signaling pathways involved in aerobic glycolysis represent a potential chemotherapeutic strategy for sensitizing leukemic cells and thereby overcoming MDR.

Efficacy and safety of 0.1% lodoxamide for the long-term treatment of superior limbic keratoconjunctivitis.

PURPOSE: To report the therapeutic efficacy and safety of topical 0.1% lodoxamide in the long-term treatment of superior limbic keratoconjunctivitis. METHODS: Sixty-seven eyes of 34 patients with active SLK were studied. Therapeutic response was analyzed according to modified-Ohashi parameters. All eyes were treated with 0.1% lodoxamide twice daily, and those with moderate or severe inflammation received a short course (7-14 days) of 0.1% fluorometholone acetate at presentation and during a relapse. Patients were evaluated at regular intervals and followed up for ≥3 months on continuous therapy. Primary endpoints included inflammatory response; rates of inflammatory control and remission; relapses while on therapy or on remission; and therapeutic failure rate. RESULTS: The mean follow-up time on lodoxamide therapy was 15.3 months. The majority of eyes (82.0%) achieved control of inflammation in a mean time of 2.2 months. Of these, 42 (76.3%) eyes remained under control while on therapy for 13.8 months. There was a significant improvement of SLK-related signs by the third month on therapy (p < 0.05). A total of 24 (35.8%) eyes achieved remission. Relapses presented in 12 (18.0%) treated eyes and in 4 (16.6%) eyes on remission. Only 5 (7.4%) eyes failed to respond to therapy. In the majority of cases (95.3%), lodoxamide 0.1% was well tolerated and minor adverse effects not requiring stopping the medication were reported in only 4.7% of patients. CONCLUSIONS: Lodoxamide 0.1% is an efficacious therapeutic alternative for the treatment of active and chronic SLK. This medication has proved to be safe and well tolerated.

A CD4 mimic as an HIV entry inhibitor: pharmacokinetics.

To date, several small molecules of CD4 mimics, which can suppress competitively the interaction between an HIV-1 envelope glycoprotein gp120 and a cellular surface protein CD4, have been reported as viral entry inhibitors. A lead compound 2 (YYA-021) with relatively high potency and low cytotoxicity has been identified previously by SAR studies. In the present study, the pharmacokinetics of the intravenous administration of compound 2 in rats and rhesus macaques is reported. The half-lives of compound 2 in blood in rats and rhesus macaques suggest that compound 2 shows wide tissue distribution and relatively high distribution volumes. A few hours after the injection, both plasma concentrations of compound 2 maintained micromolar levels, indicating it might have promise for intravenous administration when used combinatorially with anti-gp120 monoclonal antibodies.

A clinicopathological analysis of the efficacy of lodoxamide 0.1% eye drops on the conjunctiva of patients with vernal keratoconjunctivitis seen at Guinness Eye Centre, Lagos University Teaching Hospital.

OBJECTIVE: To ascertain the efficacy of Lodoxamide 0.1 in the reduction of Clinicopathological signs of the conjunctiva in Vernal Keratoconjunctivitis. STUDY DESIGN: Prospective, non-comparative, Convenient Interventional Case Series. PARTICIPANTS: One Hundred consecutive patients; 57 males and 43 females within age range 2-55 years diagnosed with active and untreated Vernal conjunctivitis were enrolled. Approval was obtained from Ethical committee of Lagos University Teaching Hospital, Idi- Araba, Lagos. METHODS: Patients were given a bottle of Lodoxamide 0.1 each to instill four times daily into both eyes. Pre-treatment Clinical photographs and conjunctival biopsies were taken in 15 volunteered patients. Ocular signs and symptoms were evaluated on day 1 (baseline), days 2-3 (Interim) and then weekly for 6 weeks (final). Post treatment Clinical photographs and conjunctival biopsies were done at the 6th week. The conjunctival tissues were fixed for 24 hours in 10 Neutral buffered formalin prior to paraffin wax embedding and routinely stained with Haematoxylin and Eosin (H & E) stains. MAIN OUTCOME MEASURE: Primary outcome was based on the reduction of inflammatory cells especially the eosinophils on histological micrographs. Secondary efficacy was based on the rate and extent of reduction of the severity scores of the clinical signs and symptoms. RESULTS: Lodoxamide 0.1 ophthalmic solution significantly reduced the density of the inflammatory cells especially eosinophils in the post treatment conjunctival biopsy cytology specimen. The mean physician severity scores for signs and symptoms consistently reduced from 72 hours of commencement of Lodoxamide with remarkable improvement in a week and complete resolution of all parameters at the end of 5th week. CONCLUSION: Lodoxamide 0.1 ophthalmic solution is highly effective in alleviating the clinical signs and symptoms of Vernal Keratoconjunctivitis and its antiallergic activity is exerted by inhibiting migration of inflammatory cells mainly eosinophlis.

Tear and serum eosinophil cationic protein levels in seasonal allergic conjunctivitis.

PURPOSE: Eosinophil cationic protein (ECP) levels in tear fluid and sera of patients with seasonal allergic conjunctivitis (SAC) were measured to assess local and systemic eosinophilic activity in SAC. The correlation between ECP levels and disease activity was evaluated. METHODS: Tears and sera were collected from 21 patients with SAC and 13 healthy control subjects. ECP levels in tears and sera were measured before and 4 weeks after treatment with 0.1% lodoxamide eyedrops. Clinical signs and symptoms of SAC were scored and the correlation of ECP levels with the clinical scores was evaluated. RESULTS: Tear and serum levels of ECP were significantly increased (p = 0.01, p = 0.02, respectively) in patients with SAC compared with the control subjects, but ECP levels were not correlated with the severity of the disease. Following treatment with topical 0.1% lodoxamide eyedrops, the mean level of ECP in tears decreased significantly (p = 0.02), whereas no significant change was observed in serum ECP levels. Furthermore, a significant decrease in clinical signs and symptoms scores was found after treatment (both p < 0.0001). CONCLUSIONS: Increased serum and tear ECP levels in patients with SAC confirms that both local and systemic eosinophil activation occurs in SAC. However, clinical signs and symptoms of SAC were not found to be correlated with the degree of eosinophilic activity. Thus ECP does not seem to have an important role in clinical manifestations of SAC.

Effects of ketotifen 0.025% and lodoxamide 0.1% on eosinophil infiltration into the guinea pig conjunctiva in a model of allergic conjunctivitis.

The effects of ketotifen and lodoxamide on eosinophil infiltration were assessed in a guinea pig model of allergic conjunctivitis. The two active treatments were coded in this masked study in which 30 male guinea pigs, sensitized to chicken egg albumin (ovalbumin), were randomly assigned to one of three groups: Group 1, instillation of 0.9% NaCl into the conjunctival sac of both eyes; Group 2, instillation of 0.025% ketotifen into the left eye and 0.9% NaCl into the right eye; Group 3, instillation of 0.1% lodoxamide into the left eye and 0.9% NaCl into the right eye. Ovalbumin was administered topically to each eye, except in Group 1 where it was only applied to the left eye. (111)In-oxine labeled eosinophils were injected into the jugular vein of each guinea pig; the animals were sacrificed 17 hours after ovalbumin had been applied. The level of radioactivity in the ketotifen- and lodoxamide-treated eyes was approximately 60% of that in the saline-treated eyes. Moreover, the mean level of radioactivity in the ketotifen- and lodoxamide-treated eyes was comparable with the mean level of radioactivity in the saline-treated eye of Group 1, which had not been exposed to allergen. These results indicate that the therapeutic effects of ketotifen and lodoxamide in allergic conjunctivitis may be partly mediated by an inhibitory effect on eosinophils.

Comparison of lodoxamide 0.1% ophthalmic solution and levocabastine 0.05% ophthalmic suspension in vernal keratoconjunctivitis.

PURPOSE: To compare the clinical efficacy and safety of lodoxamide 0.1% ophthalmic solution with levocabastine 0.05% ophthalmic suspension, each given four times daily (QID) for three months to patients with vernal keratoconjunctivitis (VKC). METHODS: The study was conducted multinationally according to a triple-masked parallel design in 95 VKC patients, with assessments at baseline then monthly during the three months of treatment. The primary efficacy variables were a Physician's Clinical Judgement Scale and a Patient's Overall Judgement Scale of improvements from baseline. Signs and symptoms of VKC were also assessed. RESULTS: Both primary efficacy variables showed significantly greater overall improvement of VKC from baseline with lodoxamide than levocabastine. The superiority of lodoxamide was demonstrated by the Physician's Clinical Judgement Scale at months 2 and 3, with a trend, at month 1, and by the Patient's Overall Judgement Scale at months 1, 2 and 3. All signs and symptoms of VKC improved significantly from baseline at all time points, regardless of treatment (p<0.001). However, relative to levocabastine, conjunctival discharge, photophobia and lacrimation were significantly reduced by lodoxamide at months 1, 2 and 3, itching at months 2 and 3, and bulbar conjunctiva at month 3. The temporal improvement of superior tarsal papillae did not differ significantly between treatments. Both were well tolerated. CONCLUSIONS: Lodoxamide 0.1% and levocabastine 0.05% eye drops, instilled four times daily for three months, were effective, safe and well tolerated by patients with VKC, but lodoxamide was significantly superior to levocabastine.

Lodoxamide as adjuvant therapy in patients with dry eye.

Dry eye, due to its impaired function of tear film becomes more susceptible to all kinds of airborne allergens. Due to air pollution this is more marked in urban areas, and is compounded by the modern way of life. There are various standard topical medications which alleviate allergic reaction of the eye, but many of them must be administered with caution and only on short term due to their potentially hazardous side effects. The purpose of this work is to assess the efficacy of lodoxamide, a new antiallergic medication for topical use, whose advantage is low or absent risk of adverse side effects, in alleviating local allergic reactions of the eye in patients with dry eye. Research has shown that, compared to treatment with eye lubricants alone (artificial tears), treatment with artificial tears combined with lodoxamide has resulted in more marked decrease in the signs of inflammation, and to the lesser extent to the reduction of the symptoms as well.

[Evaluation of efficacy and safety of sterile solution of lodoxamide in patients with ocular allergy]. / Evaluarea eficacitatii si sigurantei solutiei sterile oftalmice de lodoxamida la pacientii cu tulburari oculare alergice.

PURPOSE: Evaluating the efficiency and safety of Alomide (lodoxamide 01.%) in the treatment of allergic conjunctivitis. MATERIAL, METHOD: 12 patients have been selected during may-august 1998, in order to be treated with Alomide 4 times daily. The clinical exam of the patient included: general information, history, ocular examination. The ocular status of each patient has been evaluated with a score: the intensity of each symptom and sign has been graded between 1-3. RESULTS: In all cases, the use of Alomide induced the improvement of the typical symptoms and signs of the allergic conjunctivitis. No side effect related to the use of the drug has been noted. CONCLUSION: Due to its dual action (inhibition of both mast cells and eosinophils), Alomide covers most of the allergic response.

Mechanisms and comparison of anti-allergic efficacy of topical lodoxamide and cromolyn sodium treatment in vernal keratoconjunctivitis.

PURPOSE: To explore the mechanism of action of topical lodoxamide and cromolyn sodium treatment in vernal keratoconjunctivitis (VKC) and to compare the efficacy of these drugs to each other. DESIGN: Single-investigator, masked, randomized, clinical trial. PARTICIPANTS: Twenty male and 10 female patients between the ages of 6 and 19 years, who were diagnosed as having active VKC, were enrolled in this study. INTERVENTIONS: The patients were randomly divided into two equal groups (groups A and B). Group A patients received topical lodoxamide ophthalmic solution 0.1% (LOS); topical cromolyn sodium ophthalmic solution 4% (CSO) was prescribed to group B patients in a dose of two drops four times daily. MAIN OUTCOME MEASURES: The eye symptom severity scores and clinical signs of the patients were evaluated both in the pre- and post-treatment periods. In addition to the clinical data, conjunctival impression cytologic specimens were obtained from patients both before and after treatment. Impression cytologic specimens were stained using immunohistochemical methods to detect the percentages of CD4(+), CD8(+), CD45RA(+), and CD23(+) cells. Statistical analyses were performed within and between groups. RESULTS: The percentages of CD4(+) and CD23(+) cells in tear samples of patients in groups A and B were significantly higher in the pretreatment stage than post-treatment stage. In the post-treatment stage, group A patients had significantly lower CD4(+) and CD23(+) cell values compared with group B patients. Patient symptom scores and clinical signs were at a significantly lower level after treatment with either LOS or CSO in both groups A and B compared with their pretreatment values. Moreover, group A patients had significantly lower symptom scores and clinical signs than group B patients in the post-treatment stage. CONCLUSIONS: Clinical superiority of LOS over CSO may be linked to its greater effect on the CD4(+) cells, because CD4(+) cells plays a pivotal role in the pathogenesis of VKC.

[Alomide eyedrops in the treatment of allergic conjunctivitis and keratoconjunctivitis]. / Primenenie glaznykh kapel' "Alomid" v lechenii allergicheskikh kon''iunktivitov i keratokon''iunktivitov.

New drug lodoxamine (alomide) opens new vistas in the treatment of allergic diseases of the eyes highly prevalent both in adults and children. This drug prevents release of mast cell mediators and delays eosinophil migration to conjunctival and corneal tissue, thus exerting a spectrum of antiallergic effects. Clinical studies carried out in 170 patients demonstrated a high efficacy of alomide in the treatment of subacute and chronic pollenosis conjunctivitis, spring keratoconjunctivitis, multiple and toxic allergic keratitis, and other allergic conjunctivities. Alomide can be used as a preventive drug in patients with allergies under high-risk conditions and in patients wearing contact lenses. It is effective in combined therapy of keratitis and keratouveitis. Alomide eye drops are well tolerated.

Comparison of topical 0.05% levocabastine and 0.1% lodoxamide in patients with allergic conjunctivitis. Study Group.

PURPOSE: The aim of the study was to assess the efficacy and safety of 0.05% levocabastine eyedrops (H1 receptor blocker given BID + vehicle BID) compared with 0.1% lodoxamide ophthalmic solution (mast-cell stabilizer instilled QID) in reducing ocular signs and symptoms of allergic conjunctivitis. METHODS: A randomized, double-masked, parallel-group study was conducted in seven centres in France, in which 93 patients suffering from seasonal or perennial allergic conjunctivitis were randomly allocated to either 0.05% levocabastine (n = 47) or 0.1% lodoxamide (n = 46) in both eyes for a 14-day period. Efficacy was evaluated by subjective (prickling, burning, photophobia, itching) and objective (redness, chemosis, eyelid edema, tearing) sign scores at visits on days 7 and 14, and from data noted daily by the patient in a self-evaluation form. Safety was assessed as tolerance upon instillation and adverse event reports. RESULTS: The ocular allergy symptom and sign scores were comparable in the two treatment groups at baseline. With time, statistically and clinically significant reductions (p < 0.001) from baseline were observed for the subjective and objective scores, with no difference between the treatment groups. After the first instillation, signs were alleviated more rapidly in levocabastine-treated patients than in the lodoxamide group (p < 0.001). Overall assessments by the patient and investigator were similar in both groups. No serious adverse events were reported. CONCLUSIONS: Levocabastine ophthalmic suspension 0.05% (BID) appears to be as effective and safe as lodoxamide 0.1% (QID) in the management of allergic conjunctivitis.

Efficacy of lodoxamide eye drops on mast cells and eosinophils after allergen challenge in allergic conjunctivitis.

PURPOSE: The purpose of the study is to evaluate in a double-blind, randomized study the efficacy of lodoxamide tromethamine 0.1% versus placebo. METHODS: Signs and symptoms, tear tryptase, and tear fluid cytology were evaluated in 20 asymptomatic subjects with allergic conjunctivitis. The study included three allergen challenges in skin test-positive patients. At the first visit, a threshold dose of allergen was established. At the second visit, a bilateral ocular challenge was performed without pretreatment. At the third visit, either lodoxamide or placebo eye drops were used for 1 week before ocular challenge. RESULTS: Lodoxamide significantly reduced tryptase levels (P < 0.01), neutrophils (P < 0.04), and eosinophils (P < 0.01) in the tear fluid and significantly inhibited ocular itching (P < 0.02) when compared with that of placebo. CONCLUSIONS: Lodoxamide is effective in reducing tryptase levels and the recruitment of inflammatory cells in the tear fluid after allergen challenge.

Contact lens induced conjunctivitis: a model of human ocular inflammation.

PURPOSE: To demonstrate the usefulness of contact lens induced conjunctivitis as a model of human ocular inflammation and to evaluate the effect of antiallergic eyedrops on this model. METHODS: We recruited 40 subjects with contact lens induced conjunctivitis. Half were treated with ketorolac tromethamine (KT), and half with iodoxamide tromethamine (LT). Signs, symptoms, contact lens wearing time, and wearing time until discomfort developed were evaluated at baseline, day 7, and day 14. RESULTS: The group receiving LT showed improvement of symptoms 7 days after beginning the study (P = 0.016), and both the LT and KT groups showed improvement from baseline on day 14 (P = 0.001 and P = 0.004, respectively). Signs improved for both the KT group (P = 0.011) and the LT group (P = 0.043) on day 7 and day 14 (P = 0.033 and P = 0.007, respectively). Mean contact lens wearing time improved on day 14 for the group treated with KT (P = 0.001). CONCLUSIONS: Contact lens induced conjunctivitis appears to be a useful model of human ocular inflammation. Both antiallergics KT and LT improve contact lens tolerance in subjects with contact lens induced conjunctivitis. Two weeks of treatment may be required to demonstrate therapeutic benefits of antiallergic drops.

Lodoxamide in vernal keratoconjunctivitis.

Lodoxamide may be superior compared with cromolyn sodium for treatment of VKC. It is difficult, however, to conclusively determine the superiority of lodoxamide compared with cromolyn from the three studies reviewed in this article. Optimally, a triple-blind, randomized, placebo-controlled, multicenter trial involving the ophthalmic products cromolyn sodium 4%, lodoxamide 0.1%, and placebo (preferably NaCl 0.9%) with a treatment duration of at least 90 days and a similar sample size for each study group would lend the most credence to the determination of superiority of lodoxamide compared with cromolyn sodium for the treatment of VKC.

Tear histamine and histaminase during the early (EPR) and late (LPR) phases of the allergic reaction and the effects of lodoxamide.

The objectives of this study were two-fold: to identify tear histamine content and its relationship to changes in tear histaminase activity during the early (EPR) and late phases (LPR) of the allergic reaction induced by a conjunctival provocation test (CPT) and to evaluate the effects of lodoxamide on histamine release and allergic signs and symptoms during EPR and LPR. A baseline CPT was administered to 20 allergic patients with no baseline signs or symptoms of allergy. Clinical signs and symptoms were evaluated after 20 minutes and 6 hours. Tear samples were taken after 5-10 minutes and after 6 hours for subsequent analyses of cytology and histamine content (ELISA). Patients were then randomly assigned to receive lodoxamide or placebo four times daily for one week in a double-masked fashion. A second CPT was done after this therapy and the same parameters were re-evaluated. During EPR, tear histamine increased significantly with respect to baseline values (p < 0.05). During LPR, tear histamine increased significantly (p < 0.05) only in histamine inactivated samples. Histaminase enzymes were also significantly less active during the EPR (5.5 +/- 0.7) than the LPR (9.9 +/- 2.3) and at baseline. Histamine levels significantly correlated with allergic signs and symptoms (p < 0.05) only during the EPR. Lodoxamide significantly reduced histamine release during EPR (p < 0.05), allergic signs and symptoms during both EPR (p < 0.001) and LPR (p < 0.005), and tear cytology counts during LPR. In conclusion, greater histaminase activity may account for the smaller amount of tear histamine generally found during LPR, while these enzymes seem to play less of a role during the surge of histamine release and activity in the EPR. Lodoxamide was shown to ideally inhibit various aspects of the allergic reaction: clinical signs and symptoms in both the early and late phases, the primarily EPR-related peak of histamine release, and the primarily LPR-related changes in tear cytology.

Efficacy of lodoxamide 0.1% versus N-acetyl aspartyl glutamic acid 6% ophthalmic solutions in patients with vernal keratoconjunctivitis.

In a double-masked, randomized and controlled clinical trial, the effectiveness and safety of lodoxamide 0.1% eye drops were compared with N-acetyl aspartyl glutamic acid 6% (NAAGA) drops in the treatment of 120 patients with vernal keratoconjunctivitis. There were 60 patients in each of the two study groups. The drugs were instilled 4 times daily for 60 days. Follow-up examinations were made on days 7, 30 and 60. Of the 120 patients, 98 (50 in lodoxamide and 48 in NAAGA groups) were still available for follow-up on day 7, 89 (45 in lodoxamide and 44 in NAAGA groups) on day 30 and 75 (38 in lodoxamide and 37 in NAAGA groups) on day 60. Lodoxamide was clinically more effective than NAAGA. Statistically significant trends toward improvement were noted in the lodoxamide group in resolving papillae on day 30, decreasing corneal staining on days 30 and 60, relieving photophobia on day 60, tearing on days 7, 30 and 60 and itching on days 30 and 60. Lodoxamide 0.1% was more effective in lowering the mean scores for corneal staining on days 30 and 60 (p < 0.05). The composite scores for clinical signs and symptoms calculated by averaging the mean scores for signs and symptoms showed clinically significant differences in favor of the lodoxamide group. More frequent follow-up visits might have resulted in better statistical correlations. Treatment-related adverse events were reported in both groups with similar frequency but none were permanent or serious.

Lodoxamide tromethamine treatment for superior limbic keratoconjunctivitis.

PURPOSE: We studied the efficacy of topically applied lodoxamide tromethamine 0.1% in the treatment of superior limbic keratoconjunctivitis. METHODS: Three patients with clinical findings of bilateral superior limbic keratoconjunctivitis. were treated with topical lodoxamide tromethamine four times daily in both eyes. RESULTS: While the patients were taking lodoxamide tromethamine, symptoms and objective findings resolved. CONCLUSIONS: Topically applied lodoxamide tromethamine 0.1% is useful in the treatment of superior limbic keratoconjunctivitis. There may be a role for mast cell stabilizers in the treatment of this disorder.

Efficacy of lodoxamide 0.1% ophthalmic solution in resolving corneal epitheliopathy associated with vernal keratoconjunctivitis.

A multicenter, randomized, double-masked, parallel-group study compared the long-term efficacy and safety of lodoxamide 0.1% ophthalmic solution and placebo in 118 patients with vernal keratoconjunctivitis. The test drugs were instilled four times daily for 90 days. Lodoxamide 0.1% ophthalmic solution was significantly (P < .05) more effective than placebo in lowering severity scores for epithelial disease and corneal staining, evidence of the superior efficacy of lodoxamide 0.1% ophthalmic solution in reversing the corneal complications commonly associated with moderate to severe vernal keratoconjunctivitis. Additionally, lodoxamide 0.1% ophthalmic solution ameliorated the other key signs of vernal keratoconjunctivitis, including upper tarsal papillae, limbal signs (papillae, hyperemia, and Trantas' dots), and conjunctival discharge. The between-group differences in the relief of symptoms (itching, tearing, and photophobia) were clinically significant but not always statistically significant. Treatment-related adverse events were reported with similar frequency in both treatment groups, and none were serious.

Effect of lodoxamide on in vitro and in vivo conjunctival immediate hypersensitivity responses in rats.

The antiallergic compound, lodoxamide, was evaluated for its abilities to attenuate a local allergic reaction in rat conjunctiva in vivo and to inhibit rat conjunctival mast cell mediator release in vitro. Topically applied lodoxamide (0.01, 0.10 and 1.0%, w/v) dose-dependently reduced the allergic response (23, 43 and 72%, respectively) in vivo. Lodoxamide was more effective than cromolyn sodium, N-acetyl aspartyl glutamic acid (Naaxia) and levocabastine, and 25 (7-200) times more potent than nedocromil sodium in direct comparisons. Addition of lodoxamide (10 micrograms/ml) to sensitized conjunctival tissue in vitro immediately prior to antigen challenge significantly reduced the amount of histamine released by the tissue. These data suggest that lodoxamide's in vivo anti-allergic activity in the conjunctiva is associated with its ability to prevent allergic mediator release from mast cells contained in this same tissue.