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Late mortality and levamisole adjuvant therapy in colorectal cancer.

Beginning in 1975, 78 patients with resected stage B and C colorectal carcinoma were randomly assigned (2:1) to receive either levamisole 2.5 mg kg-1 day-1 given for 2 days every week for 18 months or placebo therapy in the same schedule. Pretreatment characteristics (age, gender, disease site, CEA and stage) and the pattern of follow-up were similar in both groups. For the first 5 years following randomisation, relapse-free survival and overall survival were similar in the two treatment groups. Subsequently, excess late mortality was associated with levamisole group assignment. Consequently, overall survival was somewhat greater in the placebo group than in the levamisole group, 68% vs 38% (P < 0.08). For patients surviving 5 years from randomisation, subsequent survival favoured placebo over levamisole (100% vs 57%; P < 0.03). The absolute numbers of deaths were 27 in the levamisole group (19 definitely cancer related) and seven in the group placebo (five definitely cancer related). This long-term result seen with a more intensive adjuvant levamisole dose and schedule suggests: (1) other levamisole adjuvant trials in patients with colorectal cancer should be examined for long-term outcome; (2) future trials utilising the even higher levamisole dosage required for clinical immunomodulation should proceed cautiously.

Aged↗

Levamisole treatment enhances protective antibody response to hepatitis B vaccination in hemodialysis patients.

Hemodialysis shows a high risk for hepatitis B infection, and hepatitis B virus (HBV) vaccination has now become a routine procedure. Unfortunately, 40% to 50% of hemodialysis patients do not have adequate protective antibodies against the HBV vaccination which is thought to be due to depressed cell mediated immunity. Levamisole has been reported to stimulate depressed T-cell activity and enhance B lymphocyte function and restore delayed hypersensitivity reactions in immune-depressed patients. We studied the effects of levamisole, an immunomodulatory agent, on the protective antibody response of hemodialysis patients to the HBV vaccination. Our hemodialysis patients with negative anti-HBs antibody routinely received 40 microg doses of recombinant HBV vaccine intramuscularly at 0, 1, and 6 months, and we followed serum anti-HBs levels. Patients with a serum antibody level of >10 mIU/ml were considered as responders. Study groups were classified as follows. Group 1 was comprised of 96 chronic hemodialysis patients with negative anti-HBs and HBV core antibody (52 male, 44 female, mean age of 45 +/- 15 years and mean hemodialysis duration of 46 +/- 40 months) who received HBV vaccination; 55 patients (57%) were found to be responders. Group 2 was comprised of 19 randomly selected patients who had never received hepatitis B vaccine (13 male, 6 female, mean age of 42 +/- 14 years, mean duration of hemodialysis 31 +/- 27 months) and who were started on an HBV vaccination protocol with levamisole per os 80 mg after each hemodialysis session for 4 months and followed up on serum anti-HBs levels. Seventeen of the patients completed this levamisole treatment. Fourteen of the 17 patients had the levels of the protective serum antibody indicating a higher response rate when compared with patients who did not receive levamisole (82% versus 57%, respectively, p < 0.05). Group 3 was comprised of 19 patients randomly selected from persons who did not respond to previous vaccination programs (10 male, 9 female, mean age of 51 +/- 14 years, mean duration of hemodialysis 41 +/- 31 months). A second HBV vaccination program was started with the same levamisole protocol. In this group, 18 patients completed this treatment model. Fourteen of them responded to the vaccination model. In Group 4, a second HBV vaccination program was applied without levamisole to 20 randomly selected persons who did not respond to the previous routine vaccination program (12 male, 8 female, mean age of 53 +/- 17 years, mean duration of dialysis 51 +/- 38 months). Only 3 of them responded to a second vaccination program. Comparing Group 3 with Group 4, there was a higher responder rate to HBV vaccination (77% versus 15%, respectively, p < 0.0001). These results show that levamisole treatment increases the response rate to the first HBV vaccination and of the previously unresponsive cases by modulating possible cellular immune response.

Adjuvants, Immunologic↗

Molecular basis of the differential sensitivity of nematode and mammalian muscle to the anthelmintic agent levamisole.

Levamisole is an anthelmintic agent that exerts its therapeutic effect by acting as a full agonist of the nicotinic receptor (AChR) of nematode muscle. Its action at the mammalian muscle AChR has not been elucidated to date despite its wide use as an anthelmintic in humans and cattle. By single channel and macroscopic current recordings, we investigated the interaction of levamisole with the mammalian muscle AChR. Levamisole activates mammalian AChRs. However, single channel openings are briefer than those activated by acetylcholine (ACh) and do not appear in clusters at high concentrations. The peak current induced by levamisole is about 3% that activated by ACh. Thus, the anthelmintic acts as a weak agonist of the mammalian AChR. Levamisole also produces open channel blockade of the AChR. The apparent affinity for block (190 microm at -70 mV) is similar to that of the nematode AChR, suggesting that differences in channel activation kinetics govern the different sensitivity of nematode and mammalian muscle to anthelmintics. To identify the structural basis of this different sensitivity, we performed mutagenesis targeting residues in the alpha subunit that differ between vertebrates and nematodes. The replacement of the conserved alphaGly-153 with the homologous glutamic acid of nematode AChR significantly increases the efficacy of levamisole to activate channels. Channel activity takes place in clusters having two different kinetic modes. The kinetics of the high open probability mode are almost identical when the agonist is ACh or levamisole. It is concluded that alphaGly-153 is involved in the low efficacy of levamisole to activate mammalian muscle AChRs.

Amino Acid Sequence↗

Treatment of inoperable non-small cell carcinoma of the lung with radiation therapy, with or without levamisole. A randomized trial of the Southeastern Cancer Study group.

In a randomized trial, 251 patients with inoperable non-small cell lung cancer received radiation therapy (RT) with or without levamisole (2.5 mg/kg twice weekly for 1 year, or until progression). Radiation therapy was delivered to 6000-6500 rad for Stages I and II, and 4000-4500 rad by continuous or split course for Stage III disease. Responses were observed in 40% of patients receiving placebo, and in 29% of patients taking levamisole. Relapse occurred at local sites only in 53% of the placebo- and 75% of the levamisole-treated patients. The frequency of relapse in distant sites was lower (25%) in the levamisole group as compared with the placebo group (47%). No significant difference in survival was observed between the placebo and levamisole-treated groups (median survival, 48.2 and 45 weeks, respectively). Responders to radiotherapy survived significantly longer than nonresponders (median survival, 73 vs. 33.3 weeks, p = 0.001). Among responders, the median survival of patients treated with levamisole was shorter (63.9 weeks) than that of patients receiving placebo (92.7 weeks). Toxicity attributable to levamisole included severe granulocytopenia in five patients and severe nausea and vomiting in nine. It is concluded that levamisole is without significant benefit in this setting.

Adenocarcinoma↗

A randomized placebo-controlled double-blind study of levamisole in the treatment of limited and slowly spreading vitiligo.

BACKGROUND: A previous uncontrolled, open trial of levamisole in patients with limited and slowly spreading vitiligo had shown that new lesions did not develop in 94% of patients after 2-4 months of treatment with the drug. OBJECTIVES: To assess the efficacy of levamisole in the treatment of slowly spreading, limited vitiligo. METHODS: In a randomized double-blind trial at the Department of Dermatology and Venereology, All India Institute of Medical Sciences, New Delhi, India, 60 patients with vitiligo involving < 2% of the body surface area and with slowly spreading disease (defined as one to five new lesions in the previous month or six to 15 new lesions in the previous 3 months) were randomly allocated to receive oral levamisole 150 mg or placebo on two consecutive days in a week. Children received oral levamisole 100 mg. All patients applied mometasone furoate 0.1% cream on the depigmented macules once daily. Patients were evaluated monthly for 6 months. The main outcome measure was the occurrence of new lesions, counted at each monthly visit. The secondary outcome measures comprised: (i) a dermatology-specific instrument, the Dermatology Life Quality Index or Children's Dermatology Life Quality Index questionnaires, which were completed by the patients at baseline and at every visit, and (ii) a general health questionnaire, the World Health Organization Quality of Life Brief Questionnaire, which was completed at baseline and at the end of the study. RESULTS: Forty-three patients completed 6 months of follow-up. The mean +/- SD number of new lesions that developed during the study period of 6 months was 1.9 +/- 2.0 (range 0-8) in the levamisole group and 1.8 +/- 2.0 (range 0-7) in the placebo group (P = 0.92). The proportion of patients who did not develop any further new lesions for the remainder of the study period was higher in the levamisole group at all the monthly evaluation points, although it was statistically significant (P = 0.05) only at the fourth month. Improvement in quality of life was similar in both groups. CONCLUSIONS: The study indicates that levamisole is not as effective in arresting disease progression as was observed in a previous open study. A study with a larger sample size is necessary to determine if levamisole is truly superior to placebo in this respect.

Adult↗

Interactions of levamisole with some autonomic drugs on guinea-pig vas deferens.

The effects of levamisole on responses to various agonists were studied in guinea-pig vas deferens. Levamisole did not itself exhibit any contractile or relaxant effect on guinea-pig vas deferens but in the presence of levamisole the concentration-response curve of noradrenaline (NA) was shifted to the left and the maximal response was increased. Responses to field-stimulation at 5 and 10 Hz were potentiated by levamisole. Cocaine and denervation caused potentiation of NA responses and these enhanced responses remained unchanged in the presence of levamisole. Acetylcholine (ACh) responses were potentiated by levamisole whereas responses to histamine, KCl and methoxamine remained unaltered. These results suggest that levamisole does not have any action at postsynaptic alpha-adrenoreceptors. The increased responses to NA and ACh in the presence of levamisole may be due to its uptake1, blocking and anticholinesterase activities respectively.

Animals↗

Immunomodulation by levamisole in patients with recurrent aphthous ulcers or oral lichen planus.

The purpose of this study was to evaluate the effect of levamisole on the immune system of patients with recurrent aphthous ulcers (RAU) or oral lichen planus (OLP) in an open trial. Lymphocyte subsets, serum immunoglobulins, and circulating immune complexes (CIC) in patients with RAU or OLP and in normal control subjects were determined by an indirect immunofluorescence (IIF) technique with monoclonal anti-lymphocyte antibodies, by single radial immunodiffusion, and by precipitation with 3% polyethylene glycol, respectively. In addition, the anti-nuclear antibodies (ANA) and anti-basal cell antibodies (anti-BCA) in sera were detected by an IIF technique. We found a significant improvement in clinical symptoms and normalization of the decreased CD4/CD8 ratio in RAU patients after levamisole treatment. Moreover, the decreased CD4/CD8 ratio, which persisted until the remission stage in the untreated RAU patients, reverted to normal in the active late stage in the levamisole-treated patients. This reversion of aberrant cellular immunity in an earlier stage of the ulcer cycle may explain why RAU patients experience symptom improvement after levamisole treatment. Although RAU patients treated with levamisole for 1 to 3 or 4 months still had higher than normal levels of CIC and serum immunoglobulins, the levels of their IgA and IgM returned to normal values after 4 months of levamisole treatment. The serum ANA detected in 6 patients with RAU and 3 patients with erosive OLP disappeared after 1-22 months of levamisole treatment. The disappearance of serum anti-BCA was also observed in 50% of the anti-BCA-positive patients with erosive OLP after 3-13 months of levamisole treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Levamisole exacerbates coxsackievirus B3-induced murine myocarditis.

Levamisole administration to several strains of adolescent mice at the time of or up to 4 days post-inoculation (p.i.) with a myocarditic variant of coxsackievirus B3 (CVB3m) increased the number of myocarditic lesions above that found in CVB3m-inoculated mice. Virus replication in heart tissues in vivo was not affected by levamisole administration to the mice, nor was production of neutralizing antibody to CVB3m. Lymphocytes from nodes of virus-inoculated mice treated with levamisole at 2 days p.i. exhibited an increased reactivity to phytohemagglutinin on days 6 and 8 p.i., compared with respective responses by nodal T lymphocytes from CVB3m-inoculated mice. Levamisole treatment of CVB3m-inoculated mice also increased the reactivity of splenic and peripheral blood T lymphocytes to phytohemagglutinin on day 8 p.i., but not day 6 p.i., compared with the respective responses by lymphocytes from CVB3m-inoculated mice. The proportion of theta antigen-bearing lymphocytes in the total lymphocyte population in peripheral blood of CVB3m-inoculated mice was not altered by levamisole treatment. However, CVB3m-induced reduction in this subpopulation of lymphocytes in the nodes was restored to control levels by levamisole treatment. Reactivities of cytotoxic T lymphocytes from CVB3m-inoculated mice were increased against both normal and CVB3m-inoculated target cells after levamisole treatment of these mice. The results suggest that levamisole may contribute to CVB3m induction of myocarditis by several mechanisms, such as increasing the blastogenic activity of the phytohemagglutinin-responding subset of T lymphocytes, by possibly altering T-lymphocyte distribution in the body and by nonspecifically increasing reactivities of cytotoxic T lymphocytes.

Animals↗

Possible drug interaction between warfarin and combination of levamisole and fluorouracil.

OBJECTIVE: To report a possible drug interaction between the combination of fluorouracil (5-FU), levamisole, and warfarin. CASE SUMMARY: An elderly patient with chronic atrial fibrillation and prosthetic valve replacements had been taking warfarin 22.5 mg/wk. Following the diagnosis of colon cancer (Duke's classification D), a chemotherapy regimen of 5-FU and levamisole was started. Within four weeks after initiation of chemotherapy, the International Normalization Ratio (INR) increased from 3.04 to 39.56. Warfarin was discontinued and restarted at 7.5 mg/wk. Discontinuation of levamisole and 5-FU for a five-week period resulted in the INR falling to a subtherapeutic level. Reinstitution of the chemotherapeutic regimen once again led to an increase in INR. DISCUSSION: A literature search showed no reports of an interaction between warfarin and levamisole. However, prolongation of 5-FU half-life and an increase in INR have been reported with the concurrent use of 5-FU and warfarin. Inhibition of the hepatic metabolism of warfarin by 5-FU and levamisole is the postulated mechanism of this drug interaction. CONCLUSIONS: This case describes the clinically significant increase of INR in an elderly patient after adding a chemotherapy regimen of levamisole and 5-FU to a previous regimen of warfarin alone. The increasing incidence of both atrial fibrillation and colon cancer with age could potentially require the concomitant use of 5-FU, levamisole, and warfarin. Because of the potential severity of this interaction, close monitoring of INR and warfarin dosage adjustment is recommended in patients receiving warfarin along with levamisole and 5-FU.

Aged↗

Effect of first-pass hepatic metabolism on the disposition of levamisole after intravenous administration in rabbits.

OBJECTIVE: To evaluate the contribution of first-pass hepatic metabolism of levamisole on levamisole disposition in rabbits. ANIMALS: 30 male New Zealand White rabbits. PROCEDURES: Rabbits were randomly placed into 2 groups. Rabbits in the first group received levamisole via the marginal ear vein at the following 3 doses: 12.5, 16, and 20 mg/kg (5 rabbits for each dose). Rabbits of the second group received levamisole via the jejunal vein at the same doses (5 rabbits each). During the following 240-minute period, plasma samples were obtained and quantified for levamisole concentrations by reversed-phase high-performance liquid chromatography. RESULTS: No significant differences were found between pharmacokinetic parameters calculated by compartmental or noncompartmental analysis. Mean hepatic extraction ratio ranged from -0.044 to 0.017 and from 0.020 to 0.081 when area under the plasma concentration-time curve values were obtained after compartmental or noncompartmental analysis, respectively. After compartmental analysis, plasma concentration decreased bi-exponentially. Mean pharmacokinetic parameter values were as follows for each dose (12.5, 16, and 20 mg/kg, respectively): after levamisole administration via the marginal ear vein, volume of distribution at steady state (Vss) = 4.26, 4.33, and 3.20 L/kg; total body clearance (CI) = 49.04, 43.77, and 39.26 mL/kg x min; and half-life associated with beta-phase (t1/2beta) = 77.93, 85.39, and 69.79 minutes. After levamisole administration via the jejunal vein, Vss = 4.38, 2.85, and 2.97 L/kg; CI = 48.14, 42.40, and 39.69 mL/kg x min; and t1/2b = 101.9, 76.71, and 76.13 minutes. CONCLUSIONS: Levamisole has a low degree of hepatic extraction in rabbits.

Animals↗

The disposition of 14C-levamisole in the lactating cow.

1. 14C-Levamisole 1(-)-2,3,5,6-tetrahydro-6-phenyl[U-14C]imidazo[2,1-b]-thiazole was administered orally and subcutaneously to lactating cows (8 mg/kg body weight). Urine, faeces, milk and blood samples were collected from 0-48 h after dosing and tissues were collected 48 h after dosing. 2. 14C-Labelled residues (ppm 14C-levamisole equivalents) in blood were highest at 3 h (2.2 ppm, oral dose) or 6 h (2.1 ppm, subcutaneous dose) and then declined to less than 0.5 ppm 48 h after dosing. 3. 14C-Labelled residues in milk were highest in samples collected from 0-12 h after dosing (1.55 ppm and 1.86 ppm of levamisole equivalents from oral and subcutaneously dosed animals, respectively) and declined to 0.06 ppm in milk collected from 36-48 h after dosing. Milk collected from 0-48 h after dosing accounted for 0.2% (oral dose) and 0.6% (subcutaneous dose) of the total 14C-activity administered as 14C-levamisole. The parent compound, 14C-levamisole, accounted for 12% or less (declined with time after dosing) of the total 14C-activity in the milk. Three 14C-labelled metabolites (formed by oxidation of imidazoline ring and/or opening of thiazolidine ring) in the milk were isolated and identified. 4. Urinary excretion accounted for 83% and 84% and faecal excretion accounted for 11% and 9% of the total 14C-activity given orally and subcutaneously, respectively, as 14C-levamisole. No 14C-levamisole was detected in the urine; the major urinary metabolite (formed by opening of thiazolidine ring) was isolated and identified. 5. The 14C-activity remaining in the animals 48 h after dosing was widely distributed in body tissues; however, the concentration in the liver was substantially higher than in all other tissues examined. Less than 5% of the 14C-activity in the liver was present as 14C-levamisole.

Administration, Oral↗

The effects of levamisole poisoning on the haematological and biochemical parameters in dogs.

This study was designed to evaluate possible organ and system disorders associated with experimentally induced levamisole poisoning in dogs. For this purpose, twelve clinically healthy dogs of different ages, sexes and breeds were used. They were divided into two equal groups (Group A and Group B) and given levamisole orally at a dose of 25 mg/kg of body weight daily for three days. The dogs in Group B were also injected with atropin sulphate (0.04 mg/kg of body weight) subcutaneously (sc) 1 hour after each administration of levamisole. Routine clinical examinations were made and some haematological, biochemical and blood gas parameters were established at various times after administration of levamisole. The dogs in Group A developed severe neurological signs, gastric haemorrhage, bloody vomiting, colic, anaemia and four dogs died. In Group B these signs were mild and only one dog died. Levamisole poisoning was characterised by a significant reduction in the total number of red blood cells (RBCs), concentration of haemoglobin (Hb) and packed cell volume (PCV), and by anaemia. Peripheral blood pH, actual bicarbonate of plasma (HCO3), actual base excess (BE), partial pressure of oxygen (pO2) and saturated oxygen (O2SAT) increased in both groups of animals and these dogs developed metabolic alkalosis 48 hours after the first administration of levamisole. The results of the study also show that levamisole poisoning in dogs causes a significant increase in the activity of serum alanine aminotransferase (ALT) and of alkaline phosphatase (AP) and in the concentration of urea in both Group A and Group B. In the study, atropin sulphate reduced the severity of the clinical signs and the number of deaths, but it was not alone sufficient to remedy levamisole poisoning in dogs.

Animals↗

Utility of a Haemonchus contortus/jird (Meriones unguiculatus) model for studying resistance to levamisole.

Trichostrongylid nematodes of sheep commonly are identified as exhibiting resistance to levamisole. In vitro assays have been developed to study levamisole resistance for Haemonchus contortus, but no in vivo model has been identified for this species. To determine the utility of a H. contortus/jird (Meriones unguiculatus) model for examining levamisole resistance, immunosuppressed jirds were inoculated with approximately 1,000 exsheathed infective larvae of H. contortus (resistant or susceptible to levamisole), treated per os on day 10 postinoculation (PI) with levamisole hydrochloride or analogs of the drug, and killed on day 13 PI. Stomachs were removed, opened longitudinally, incubated in distilled water at 37 C for 5 hr, fixed in formaldehyde solution, and stored for subsequent microscopic examination. Doses of levamisole and its analogs, which elicited percentage clearances of greater than or equal to 93.5 for the susceptible strain, cleared less than or equal to 68.9% of the resistant worms. These data are consistent with activities for the drugs against wild-type and levamisole-resistant strains of Caenorhabditis elegans. Thus, the H. contortus/jird model provides a useful in vivo tool to study resistance to levamisole and possibly other anthelmintics.

Animals↗

Effects of levamisole on normal and malignant murine lymphocytes.

Levamisole enhanced transformation of murine lymphocytes stimulated either by mitogens or allogeneic lymphocytes. In a similar dose-dependent pattern it stimulated in vitro growth of L1210, P1798, and 6C3HED but not YAC lymphoma cells. Stimulation of growth of lymphoma cells was greater by peritoneal cells harvested from normal mice 4 days after levamisole injection than by peritoneal cells from untreated mice. This effect correlated with the shortened survival time of BALB/c mice treated with levamisole prior to P1798 implantation compared to that of a control group not pretreated. Administration of levamisole with iodoacetamide-modified tumor cells in immunoprophylaxis studies had no effect on the rejection of a tumor implant or on development of tumor-specific antibody. Levamisole was added to regimens involving asparaginase therapy of 6C3HED-bearing C3H mice and chemoimmunotherapy of BALB/c mice bearing P1798 with methotrexate and iodoacetamide-modified P1798 cells. In neither case were there increased numbers of survivors, and mean survival time was generally decreased for the levamisole-treated groups. The stimulated tumor growth may have been mediated by a direct effect of levamisole on the lymphoma cells, through an effect on other cell types, or by both effects; these effects apparently outweighed potentially beneficial effects of levamisole on the immune system.

Animals↗

Levamisole in the treatment of Hodgkin's disease.

In vitro and in vivo action of levamisole has been studied in patients with Hodgkin's disease. In vitro levamisole significantly increased the active T cell count of 35 untreated active patients, of those being in complete remission after treatment and of 19 healthy controls; it significantly raised the total T cell count of patients. However, levamisole could not further improve the considerably increased active and total spontaneous rosette formation resulting from in vivo levamisole treatment. Twenty patients with Hodgkin's disease, being in complete remission, were given levamisole for 3 or 6 months, according to 2 different schedules. Levamisole (150 mg) given on 3 consecutive days of every second week for 3 months considerably increased the number of positive skin tests (from 8/60 to 29/60), the numbers of active and total T cells with unchanged absolute lymphocyte count, and decreased the quantity of circulating immune complex. Continuation of treatment for another 3 months resulted in slight, but consistent, decline in all the above parameters; the ratio of active T cells significantly decreased. This decline was even more pronounced if a raised larger dosage of levamisole was administered for 6 months. In the course of the treatment no side-effect or complication was observed. Levamisole is able to improve the weak cellular immune reactivity of patients with Hodgkin's disease, it can, however, result in undesired suppression in the case of too long treatment with high dose.

Adult↗

[The effect of levamisole on non-resected lung cancer--the results of randomized controlled study].

The effect of levamisole in the treatment of 61 non-resected lung cancer-26 squamous cell ca., 8 adenocarcinoma, 13 large cell ca. and 14 small cell ca- was studied by a randomized controlled trial. Levamisole was given at a daily dose of 150 mg per body weight for 3 consecutive days every 2 weeks. The main therapy, combining polychemotherapy and radiotherapy of standard dose or low dose, was given to both levamisole and control groups. The survival rate of the levamisole group was superior to that of the control group, with median survival time of 52 weeks in the former and 36 weeks in the latter, and with significant difference (p less than 0.05) during 46th to 52nd weeks. Comparing between the selected cases, the levamisole group was significantly superior (p less than 0.05) to the control group in all course examined, with median survival time of 64 weeks in the former and 36 weeks in the latter. Levamisole was more effective in the group of squamous and adenocarcinoma than large and small cell carcinoma. In the group where PPD reaction was negative at the time of initiation of the treatment levamisole was more effective than in the group of PPD positive, and also more effective in non-responders to the main therapy than responders. No side effect such as agranulocytosis was observed. Summarizing the present study, an immunotherapy employing levamisole combined with chemo-radiotherapy for non-resected lung cancer could be said to be effective in prolongation of survival time.

Adenocarcinoma↗

Controlled and clinical evaluations of the anthelmintic activity of a levamisole pour-on formulation against gastrointestinal nematodes in cattle.

Beef-type calves (n = 107) with naturally occurring helminth infections were used in a series of 3 controlled experiments to study the anthelmintic activity of a new pour-on formulation of levamisole. In the 1st experiment, the efficacy of a single treatment of levamisole pour-on at a rate of 10 mg/kg of body weight was determined, using a placebo pour-on in a similar volume as a control. In the 2nd experiment, calves were treated with levamisole pour-on at doses 0 (nontreated control), 7.5, 10, or 12.5 mg/kg of body weight. In the 3rd experiment, the anthelmintic efficacy of the optimal dose of levamisole pour-on (10 mg/kg of body weight) was compared with that of injectable levamisole at the recommended rate (6 mg/kg of body weight). In all 3 studies, levamisole pour-on, at a dosage of 10 mg/kg of body weight, was efficacious (90% to 100%) against the adult forms of Trichostrongylus axei, Haemonchus placei, Ostertagia ostertagi, Cooperia spp, Oesophagostomum radiatum, Nematodirus spp, and Bunostomum phlebotomum. Efficacy was moderate to good against Capillaria bovis, and poor or inconsistent against Strongyloides papillosus and Trichuris ovis. Clinical tests of anthelmintic efficacy and local tolerance of levamisole pour-on were conducted in 371 beef and dairy cattle in Mexico. Fecal egg counts were consistently reduced 2 weeks after a single application of levamisole pour-on at a dosage of 10 mg/kg of body weight. Local reactions were limited to various degrees of dry hair coat for up to 2 weeks at the application site. Hair loss or skin abnormalities were not observed in any of the treated cattle.

Animals↗

Regulation of human natural killing by levamisole.

The effect of levamisole on human natural killing (NK) has been studied. In short-term chromium release assays, levamisole at a concentration of 10(-3) M was inhibitory to NK when present in the assays. Pretreatment of NK effector cells and K562 target cells with levamisole separately indicated that the effect was on effector cell activity and was not due to any change in target cell susceptibility. Inactivation of the effector cells required greater than 4 h pretreatment with levamisole if NK activity was subsequently tested in the absence of the drug. Pretreatment with levamisole for up to 19 h had no effect on the lymphocyte proliferative response to phytohemagglutinin (PHA). NK activity of drug-inactivated effector cells recovered after further incubation in levamisole-free medium. Levamisole at 10(-4) M or less had no effect on NK either by pretreatment or by its presence in the NK assays.

Cell Line↗