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PubMed1984

Anthelmintic efficacy, safety, and residue evaluation of levamisole gel formulation in cattle.

Anthelmintic efficacy, safety, and residue studies were conducted in beef calves using a levamisole gel formulation. The effectiveness of levamisole gel and tablet formulations was studied in 30 calves with experimental infection of Ostertagia ostertagi. Removal of 33- to 34-day-old O ostertagi was 99.6% and 97.7%, for the gel and tablet formulation, respectively, when administered orally to supply 8 mg of levamisole HCl equivalent/kg of body weight. A comparative blood concentration study was also used to demonstrate bioequivalence of the levamisole gel to the tablet formulation. In a cross-over-designed test, 5 cattle/treatment group were dosed orally with levamisole 11.5% gel or levamisole tablets at the dosage rate of 8 mg of levamisole HCl/kg. Blood levamisole values were similar with the levamisole gel and tablet formulations. In a safety study, 3 groups of 6 calves each were given levamisole gel orally to provide 8, 24, or 40 mg of levamisole HCl/kg. A 4th group served as controls. Adverse clinical signs were not observed in cattle treated with the recommended dosage level of 8 mg/kg. Transient salivation was noticed in 1 placebo control calf, 2 calves given 24 mg/kg, and 4 calves given 40 mg/kg. Edible tissues from cattle given a single oral dose of levamisole gel (8 mg/kg) were analyzed for drug residues 2 hours and 2, 3, 5, and 7 days after treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2005

Experience with levamisole in frequently relapsing, steroid-dependent nephrotic syndrome.

This was a controlled prospective study on the use of an immunomodulator drug, levamisole, in the treatment of frequently relapsing, steroid-dependent (FR/SD) idiopathic nephrotic syndrome. The study was started on 1 January 2001 and completed on 31 December 2003. There were two groups: a treatment group who received levamisole (2.5 mg/kg) on alternate days for 1 year and a control group who received low-dose prednisolone only (<0.5 mg/kg) on alternate days for 1 year. There were a total of 56 patients (32 in the treatment group and 24 in the control group). The male to female ratio was 1.66:1 in both groups. The mean age upon initial diagnosis was 3.3 years in the levamisole group versus 4.3 years in the control group. The mean duration from diagnosis to the start of the second line treatment was 3.2 years in the levamisole group versus 2.8 years in the control group. The relapse rate and the total cumulative dose of prednisolone during the year prior to second line therapy was compared to that during the year following the institution of second line therapy in 56 patients. The mean relapse rate was reduced more significantly in the levamisole group. It was reduced by 0.29 versus 0.11 relapses/patient/month in the control group (P =0.0001). The mean cumulative dose of steroids was also reduced more significantly in the levamisole group. It was reduced by 293 versus 102 mg/m(2)/month in the control group (P <0.0001). Therapy failure was seen in 3/32 (9.4%) in the levamisole group versus 12/24 (50%) in the control group. Of the patients, 20/32 (62.5%) using levamisole were relapse-free in the follow-up year post therapy, while no patient was relapse-free in the control group over the same period. No major adverse effects of levamisole were seen. The cost of levamisole therapy was estimated to be US$ 25 per year for a 20-kg body weight child. Thus, we concluded that levamisole is a highly efficacious, safe and easily affordable initial therapy for FR/SD idiopathic nephrotic syndrome.

Adjuvants, Immunologic↗
PubMed1995

Mechanism of synergy of levamisole and fluorouracil: induction of human leukocyte antigen class I in a colorectal cancer cell line.

BACKGROUND: The use of the combination of fluorouracil (5-FU) and levamisole has been shown to improve the survival of patients with resected Dukes' stage C colon carcinoma. 5-FU is incorporated into RNA, which results in aberrant processing and turnover of RNA. Neither the mechanism of synergy between the two drugs nor the precise molecular mechanism of action of levamisole is known. Each drug has previously been shown to alter the expression of class I human leukocyte antigens (HLA class I) in colorectal cancer cell lines. PURPOSE: The purpose of this study was to explore the mechanism of interaction between 5-FU and levamisole by investigating the effect of this combination on HLA class I gene expression in the colorectal cancer cell line WiDr. METHODS: WiDr cells were treated either with 5-FU alone or with 5-FU and levamisole. Expression of HLA class I antigens was analyzed by flow cytometry using the monoclonal antibody W6/32. Specific DNA probes for HLA class I, beta 2-microglobulin, beta-actin, HLA class II, and p53 (also known as TP53) were used in Northern blot analysis of the steady-state level of messenger RNAs (mRNAs) and for "run-on" transcription analysis. RESULTS: 5-FU alone produced more than 50% increases in the expression of the HLA class I antigens, and levamisole caused a further 8%-18% increase. 5-FU caused the steady-state level of HLA class I mRNAs to increase by about 80%, and levamisole enhanced this effect of 5-FU by a further 70%. 5-FU did not increase the other mRNAs. In vitro run-on transcription revealed that 5-FU caused a 20%-57% reduction in RNA synthesis, while levamisole caused a 30%-190% increase in RNA synthesis. Levamisole therefore reversed the inhibition of RNA synthesis caused by 5-FU. Both drugs had a general effect on RNA synthesis that was not restricted to HLA class I transcription. CONCLUSIONS: The apparent synergy between levamisole and 5-FU is a result of the incorporation of 5-FU, which may stabilize HLA class I mRNAs, leading to their accumulation, while levamisole augments the accumulation of these stable mRNAs by increasing the rate of transcription. IMPLICATIONS: Levamisole reduces the toxicity of 5-FU caused by generalized inhibition of RNA synthesis, and at the same time augments the effects of 5-FU, which may be due to selective stabilization of certain mRNAs.

Blotting, Northern↗
PubMed1991

Immunological effects of levamisole in vitro.

Levamisole, an anthelminthic drug with immunological properties, has recently been reported to have antitumor activity when administered with 5-fluorouracil in patients with Duke's C colorectal carcinoma. The mechanism of this antitumor effect is unknown, but has been postulated to be related to levamisole's immunomodulatory properties. To define further the immunomodulatory activities of levamisole, we studied the in vitro effects of levamisole on monocyte and lymphocyte cytotoxicity, activation, and proliferation; induction of cytokine-induced proteins; and expression of tumor-associated antigens. Experiments utilized peripheral blood mononuclear cells from normal donors incubated in the presence of increasing concentrations of levamisole (0.1 to 100 micrograms/ml). Levamisole had no consistent effect on induction of 2',5'-oligoadenylate synthetase activity or indoleamine-2,3-dioxygenase activity, or production of tumor necrosis factor. Levamisole had no effect on monocyte cytotoxicity or expression of HLA-DR, HLA-DQ, HLA-DP, and the Fc receptor. Similarly, levamisole had no significant effect on NK or LAK cytotoxicity or the immunological activation of T-lymphocytes, assessed by expression of CD3, CD4, CD8, CD16, CD25, and CD56. Proliferation of lymphocytes from normal donors, patients with benign polyps, and patients with malignancies, with or without IL-2 or irradiated LS174T cells, was not significantly increased overall. No significant enhancement in the expression of three tumor-associated antigens (880364, NRCO-4, and ING-1) and the intercellular adhesion molecule-1 (ICAM-1) antigen on four human cancer cell lines was observed following in vitro exposure to levamisole. We conclude that levamisole is not a potent modulator of the immune parameters we examined, and that the mechanism behind the unique clinical interaction between levamisole and 5-fluorouracil in colorectal carcinoma remains to be identified.

2',5'-Oligoadenylate Synthetase↗
PubMed1980

Toxicity and drug interactions of levamisole.

Clinical signs and lesions of levamisole toxicosis include: nausea, vomiting, increased salivation, frequent urination and defecation, colic, dizziness, headache, muscle tremors, ataxia, anxiety, hyperesthesia with irritability, clonic convulsions, depression, rapid respiration, dyspnea, prostration, collapse, hemorrhages in the subepicardium and thalamus, enteritis, hepatic degeneration and necrosis, and splenic congestion. Most of these signs and lesions are similar to those observed in nicotine poisoning. Levamisole causes vasopressor and panting effects which are blocked by ganglionic blocking agents hexamethonium and mecamylamine but are not blocked by atropine. The vasopressor effect of levamisole is blocked by alpha-adrenergic antagonists phentolamine and dibenamine; however, the respiratory effect of levamisole is not affected by these alpha-adrenergic antagonists. Repeated IV injections of levamisole cause a tachyphylactic response. With levamisole-induced tachyphylaxis, the effects of other ganglionic stimulants dimethylpiperazinium and nicotine are also abolished. Levamisole causes an electroencephalographic arousal which is antagonized by atropine sulfate and mecamylamine. There is also a structural similarity of levamisole to nicotine. These studies suggest that levamisole is a nicotine-like compound. Possible treatment of levamisole poisoning is discussed. Drug interactions of levamisole with organophosphates and anthelmintics, eg, pyrantel, methyridine, and diethylcarbamazine, are also discussed.

Animals↗
PubMedDate not supplied

Novel assay and pharmacokinetics of levamisole and p-hydroxylevamisole in human plasma and urine.

A new gas chromatographic method was developed for the quantification of levamisole in human plasma and urine, using a nitrogen-phosphorus flame ionization detector. The adsorption of the drug onto glass was prevented by treating the glassware with a siliconizing agent. The sensitivity of the assay was 10 ng ml-1 and as low as 2 ng ml-1 can be detected in plasma. The urinary metabolite p-hydroxylevamisole was analysed by high performance liquid chromatography with ultraviolet detection. The sensitivity of this assay was 0.50 micrograms ml-1. Plasma and urinary concentrations of levamisole were determined in 10 healthy volunteers including seven men and three women following the administration of a single 150 mg dose of levamisole. Levamisole was rapidly absorbed (tmax 1.5 h), giving a peak plasma concentration of 716.7 +/- 217.5 ng ml-1. The plasma elimination half-life of levamisole was 5.6 +/- 2.5 h. Only 3.2 +/- 2.9 per cent of the oral dose was recovered as unchanged drug in the urine, suggesting the importance of clearance of levamisole by routes other than the kidney, and most probably by hepatic metabolism. The urinary concentrations of p-hydroxylevamisole were determined before and after hydrolysis of the urine samples with beta-glucuronidase, and the level of conjugation of the metabolite with glucuronic acid was then estimated. Cumulative recovery of the metabolite accounted for 1.6 +/- 1.1 per cent and 12.4 +/- 5.5 per cent of the oral dose of levamisole before and after hydrolysis, respectively, indicating that p-hydroxylation is a relatively important route of metabolism of levamisole, and that the p-hydroxylated metabolite is excreted mainly in conjugation with glucuronic acid. Except for the absorption rate of levamisole which is approximately twice as rapid in women as in men, there is no marked difference in the pharmacokinetics of levamisole between healthy men and women.

Adult↗
PubMed2000

Pharmacokinetics of levamisole in cancer patients treated with 5-fluorouracil.

PURPOSE: To investigate the pharmacokinetics of levamisole and a metabolite, p-hydroxylevamisole in patients with colorectal cancer treated with 5-fluorouracil (5-FU). METHODS: Following an intravenous bolus dose of 5-FU, 20 patients with colorectal cancer received oral doses of 50 mg levamisole every 8 h for 3 days. Immediately after the last dose, blood and urine samples were collected over at least an 8-h period. Samples were assayed for levamisole and p-hydroxylevamisole by GC/MS. The levamisole plasma and urine data were subjected to pharmacokinetic analysis using NONMEM software. RESULTS: Substantial interpatient variability was observed in the levamisole plasma concentration-time curves. Patients with cardiovascular or gastrointestinal complications demonstrated altered absorption of levamisole. Pharmacokinetic parameter values for levamisole were similar to those obtained previously in healthy subjects and other cancer patients. CONCLUSIONS: There is no evidence that the pharmacokinetics of levamisole are altered by 5-FU administered immediately prior to levamisole administration. The relationship between the substantial intersubject variability in levamisole plasma concentration-time curves and clinical outcome following 5-FU/levamisole adjuvant chemotherapy should be examined.

Adjuvants, Immunologic↗
PubMed1998

Clinical and pharmacokinetic studies of high-dose levamisole in combination with 5-fluorouracil in patients with advanced cancer.

PURPOSE: To determine the maximum tolerable dose (MTD) and activity of levamisole administered concurrently with 5-fluorouracil (5-FU) in a standard 5-day course. To determine the pharmacokinetics of levamisole during the course of treatment. PATIENTS AND METHODS: Levamisole was administered to 38 patients orally three times a day for 5 days concurrently with a course of 5-FU administered daily by rapid intravenous injection for 5 days. Toxicity was evaluated in 20 patients who received escalating doses of levamisole. The activity of the combination was evaluated in 18 patients who received levamisole at the MTD with 5-FU. The pharmacokinetics of levamisole were characterized in ten patients at the MTD level. RESULTS: Intractable vomiting, confusion and vertigo were the major dose-limiting toxicities. The MTD of oral levamisole was 100 mg/m2 administered three times a day concurrently with 450 mg/m2 per day intravenous 5-FU for 5 consecutive days. Partial responses lasting 5 and 11 months were observed in 2/18 patients with measurable disease at the MTD. Peak plasma concentrations of 1 microg/ml (range 0.6-1.3 microg/ml) were achieved 90 min (range 60-360 min) after an oral dose of 100 mg/m2 levamisole with a 3.5-fold accumulation noted following 4 days of administration. Peak plasma concentrations of p-hydroxylevamisole were about 5% of parent drug. Little parent drug (2-5%) was detected in urine. CONCLUSIONS: Levamisole may be administered safely with 5-FU at doses which are up to four to five times greater than those presently given in conventional regimens. The recommended dose of levamisole combined with 5-FU for future research protocols is 75 mg/m2 t.i.d for 5 days.

Adult↗
PubMed2002

Levamisole: adjunctive therapy in steroid dependent minimal change nephrotic children.

In children with minimal change nephrotic syndrome (MCNS), the steroid dependent group constitutes an especially difficult case for management. Patients in this group are prone to serious steroid side effects. Additionally, alkylating agents commonly fail to maintain remission and expose patients to more side effects. Therapy with the immunostimulant drug levamisole may therefore be another option in the attempt to maintain remission with minimal side effects. We prospectively treated 20 of our steroid dependent primary MCNS patients with levamisole. All patients were children, with an age range of 3-15 years; 16 were boys and 4 were girls. Remission was firstly induced by steroids, then levamisole was added in a dose of 2.5 mg/kg body weight on alternate days for 6 months. During this period we attempted to withdraw steroids completely and maintain patients on levamisole alone. We followed up our patients for the occurrence of relapse and side effects during this period and for a further 6 months after stopping levamisole. In 11 out of 20 children (55%), we successfully stopped steroids for more than 2 weeks. At the end of the 6-month treatment period (i.e. after 4 months of steroid discontinuation), ten patients (50%) were maintaining remission on levamisole alone. At the end of the 12-month study period (i.e. after 6 months of levamisole discontinuation), five patients (25%) were still in remission without any treatment for the previous 6 months. No significant side effects were reported during levamisole therapy. None of the patients developed neutropenia, but the leukocyte count showed a significant reduction in those who responded to levamisole treatment. We concluded that levamisole therapy for 6 months is a safe and perhaps effective therapy in a subset of children with steroid dependent MCNS to enable an otherwise infeasible withdrawal of steroids. This may be worth a trial before other types of more hazardous adjunctive therapies are considered.

Adjuvants, Immunologic↗
PubMed2004

Long-term effects of levamisole treatment in childhood nephrotic syndrome.

The effects of levamisole treatment on long-term outcome were evaluated in a retrospective study of frequently-relapsing (FRNS, n=15), steroid-dependent (SDNS, n=13), and steroid-resistant (SRNS, n=6) nephrotic syndrome in 34 children (21 boys, 13 girls, mean age 5.0+/-3.4 years) during a 60-month follow-up period. The definition of frequent relapses was > or = 4 relapses per year. The current relapse was treated with prednisolone 60 mg/m2 per day for 4 weeks, then with 40 mg/m2 every other day for 4 weeks, after which the dose was tapered by 10 mg weekly. From the beginning of the 5th week, levamisole was introduced at a dose of 2 mg/kg per day. The duration of levamisole treatment was 17+/-7 months. Before starting levamisole treatment the mean level of proteinuria was 2.17+/-1.34 g/day and the relapse rate was 4.41/year. By the end of levamisole therapy, proteinuria had fallen to 0.142+/-0.211 g/day and the relapse rate to 0.41/year. No relapse occurred in 23 of the 34 patients during levamisole treatment. In the 24-month follow-up period after the discontinuation of levamisole, 28 children remained in total remission, while 6 had relapses. The cumulative steroid dose before levamisole therapy was 7,564.4+/-3,497.1 mg/year and following the introduction of levamisole 1,472.9+/-1,729.9 mg/year (P<0.0001). We observed reversible neutropenia in 5 patients, but no other side effects were seen. Our findings suggest that in FRNS and SDNS levamisole significantly reduces both the relapse rate and the cumulative steroid dose; therefore, it could be recommended for these patients. In SRNS patients it has also some benefit because proteinuria and the cumulative steroid dose could be reduced significantly.

Adjuvants, Immunologic↗
PubMed2005

acr-16 encodes an essential subunit of the levamisole-resistant nicotinic receptor at the Caenorhabditis elegans neuromuscular junction.

The Caenorhabditis elegans neuromuscular junction (NMJ) contains three pharmacologically distinct ionotropic receptors: gamma-aminobutyric acid receptors, levamisole-sensitive nicotinic receptors, and levamisole-insensitive nicotinic receptors. The subunit compositions of the gamma-aminobutyric acid- and levamisole-sensitive receptors have been elucidated, but the levamisole-insensitive acetylcholine receptor is uncharacterized. To determine which of the approximately 40 putative nicotinic receptor subunit genes in the C. elegans genome encodes the levamisole-resistant receptor, we utilized MAPCeL, a microarray profiling strategy. Of seven nicotinic receptor subunit transcripts found to be enriched in muscle, five encode the levamisole receptor subunits, leaving two candidates for the levamisole-insensitive receptor: acr-8 and acr-16. Electrophysiological analysis of the acr-16 deletion mutant showed that the levamisole-insensitive muscle acetylcholine current was eliminated, whereas deletion of acr-8 had no effect. These data suggest that ACR-16, like its closest vertebrate homolog, the nicotinic receptor alpha7-subunit, may form homomeric receptors in vivo. Genetic ablation of both the levamisole-sensitive receptor and acr-16 abolished all cholinergic synaptic currents at the NMJ and severely impaired C. elegans locomotion. Therefore, ACR-16-containing receptors account for all non-levamisole-sensitive nicotinic synaptic signaling at the C. elegans NMJ. The determination of subunit composition for all three C. elegans body wall muscle ionotropic receptors provides a critical foundation for future research at this tractable model synapse.

Action Potentials↗
PubMed2005

Levamisole residues in chicken tissues and eggs.

Levamisole is currently being used to treat capillaria infection in chickens even though there is no published withdrawal information available for levamisole in chickens. Tissue residue withdrawal of levamisole in chickens was studied in 32 healthy broiler breeder chickens at the age of 32 wk (peak of egg production). Levamisole residues in chicken tissues, eggs, and plasma were determined by HPLC with ultraviolet (UV) detection at 225 nm. The highest level of residue and longest withdrawal after oral administration of 40 mg/kg levamisole to chickens was in the liver. On d 3 the level of levamisole were undetectable in the plasma. On d 9, levamisole residue in eggs was 0.096 microg/g and on d 18 it was 0.06 microg/g or less in all the analyzed chicken tissues. Those levels were lower than the recommended maximum residue limit (MRL). The withdrawal time for levamisole in chickens was longer than for other species tested, which is due in part to a larger dose of levamisole being recommended for chickens. In conclusion from this research, 9 d are needed for levamisole in eggs to be less than the MRL, and 18 d of withdrawal are needed before medicated birds are slaughtered if their tissues are to be safe for human consumption.

Animals↗
PubMed1991

Levamisole in the adjuvant treatment of colon cancer.

The chemistry, pharmacology, pharmacokinetics, assay methodologies, adverse effects, and dosage of levamisole are described, and the clinical studies of levamisole therapy in patients with colorectal carcinoma are reviewed. Levamisole is a synthetic, orally active agent that has antihelmintic and immunomodulatory properties. It is capable of inducing T-cell differentiation and restoring depressed effector functions of peripheral lymphocytes and phagocytes to normal. The drug is well absorbed from the gastrointestinal tract after oral administration and is extensively metabolized by the liver. Gas chromatography and high-performance liquid chromatography are the most common methods used to measure concentrations of levamisole in biologic fluids. Levamisole combined with fluorouracil has been associated with a one-third reduction in recurrence and risk of death in patients with surgically resected Dukes stage C colon cancer; this combination is now recommended as standard therapy in these patients. Uses in patients with rectal carcinoma, Dukes stage B colon cancer, metastatic colon cancer, other malignancies, or nonmalignant disorders remain investigational. Common adverse effects include nausea, abdominal pain, vomiting, diarrhea, metallic or altered taste, flulike symptoms, mood elevation, insomnia, hyperalertness, dizziness, and headache. The most serious adverse effect associated with levamisole is granulocytopenia. The FDA-approved dosage of levamisole is 50 mg orally every eight hours for three days every two weeks. Levamisole therapy is to be initiated no earlier than 7 and no later than 30 days after surgery and is to be continued for one year. Levamisole combined with fluorouracil has been associated with a one-third reduction in recurrence and risk of death in patients with resected stage C colon cancer. Further research is needed to more clearly define the mechanism of action, optimum dose and scheduling, and clinical efficacy of levamisole in treating other malignancies.

Adenocarcinoma↗
PubMed1987

Comparative local anaesthetic and antiarrhythmic actions of levamisole hydrochloride and lignocaine hydrochloride.

Using the guinea-pig wheal preparation for determining the degree of infiltration anaesthesia, lignocaine was found to be 2 times more potent than levamisole. Lignocaine was, however, 1.27 times more toxic than levamisole in the mouse. It is suggested that levamisole could be used as a local anaesthetic agent for infiltration anaesthesia. As regards surface anaesthesia, lignocaine was 16.6 times more potent than levamisole. Levamisole would, therefore, not be of use in surface anaesthesia. Levamisole was more effective than lignocaine in protecting toads against deaths due to the minimum dose of ouabain which caused 100% mortality. The therapeutic indices for levamisole and lignocaine were 4.57 and 1.58 respectively. Unlike with lignocaine it was possible to achieve more than 50% protection with levamisole. Levamisole was, however, only marginally more effective than lignocaine in reverting to sinus rhythm, barium chloride-induced ventricular dysrhythmia in the rat. It is suggested that levamisole could have potential value as an antiarrhythmic agent.

Anesthetics, Local↗
PubMed1987

Efficacy, safety, and residue evaluation of levamisole gel formulation in sows.

Anthelmintic efficacy, safety, and residue studies were conducted in sows and gilts with a levamisole gel containing 11.5% levamisole HCl. In 12 sows and 12 gilts, 8 mg of levamisole HCl equivalent/kg of body weight orally was 100% (resinate) and 91.1% (gel) effective against 55-day-old Ascaris suum and 100% (gel) and 96.1% (resinate) effective against Oesophagostomum dentatum. In 20 sows given levamisole gel (8 mg of levamisole HCl/kg) orally just before breeding, 4 to 6 weeks after breeding, 4 to 6 weeks before farrowing, and just before farrowing, there were no adverse effects. Transient salivation was noticed in five sows after treatment. In 4 groups of 4 sows each given levamisole gel orally to provide 8, 24, 40, or 80 mg of levamisole HCl/kg, adverse clinical signs were not observed in sows treated with 8 mg/kg. Transient salivation was noticed in one sow given 24 mg/kg, two sows given 40 mg/kg, and four sows given 80 mg/kg. Multiple emesis and chomping occurred in one sow given 80 mg/kg. Levamisole residues in edible tissues from sows given 8 mg of levamisole gel/kg orally were less than 0.1 mg/kg of muscle and fat in sows killed on posttreatment day (PTD) 3 and less than 0.1 mg/kg of kidney in sows killed on PTD 5. Liver residues averaged 0.78 mg/kg in sows killed on PTD 3 and were reduced to 0.31 mg/kg in sows killed on PTD 5. The 99% upper tolerance limit with 95% confidence on the withdrawal time to assure levamisole residues of less than 0.10 mg/kg in liver tissue was 11 days.

Administration, Oral↗
PubMed1981

Chemoimmunotherapy with levamisole in acute lymphoblastic leukemia.

Patients with acute lymphoblastic leukemia (ALL) who were in two consecutive protocols and in complete remission (CR) with maintenance therapy, were randomized to receive or not receive levamisole. A total of 15 of 55 low-risk patients of protocol 10-LLA-72 with levamisole had relapses, compared with 25 of 54 not receiving levamisole; 67 and 49%, respectively, remain in CR at 48 months (P less than 0.025). In protocol 1-LLA-76, 14 of 91 low-risk patients on levamisole and 25 of 93 patients receiving levamisole had relapses; 78 and 61%, respectively, remain in CR at 36 months (P less than 0.05). Seventeen of 39 high-risk patients (children with a leukocyte count higher than 50,000 and adults) receiving levamisole had relapses compared with 37 of 61 not on levamisole. The DNCB skin test showed at 18 and 24 months a 74 and 85% positivity in the levamisole groups vs. a 38 and 35% positivity in the control group (P less than 0.025). We conclude that levamisole prolongs the duration of CR and survival in low-risk patients with ALL.

Adolescent↗
PubMed1987

Treatment of fish parasites. 2. Effects of praziquantel, niclosamide, levamisole-HCl, and metrifonate on monogenea (Gyrodactylus aculeati, Diplozoon paradoxum).

In research for successful treatment of fish parasitized by monogeneans, four substances (Praziquantel, Niclosamide, Levamisole-HCl, and Metrifonate) were tested in vivo against Gyrodactylus aculeati parasitizing the skin of sticklebacks (Gasterosteus aculeatus). Fish were incubated in water containing different solutions of the drugs. Praziquantel, Niclosamide and Levamisole-HCl were effective against Gyrodactylus aculeati. Praziquantel caused irreversible lesions in the parasite tegument (beginning with 1 microgram/ml and 90 min exposure). Niclosamide was effective in a narrow concentration range of 0.075-0.1 microgram/ml (90 min). Levamisole-HCl was effective in a concentration range of 20-50 micrograms/ml for 120 min. Like Praziquantel, Niclosamide and Levamisole-HCl led to damage of the parasite tegument. The opisthaptor region and the openings of the cephalic glands were most severely affected. Furthermore, the effects of Niclosamide, Levamisole-HCl and Metrifonate on Diplozoon paradoxum parasitizing the gills of chubs (Squalius cephalus) and breams (Abramis brama) were investigated. Levamisole-HCl (10 micrograms/ml) and Niclosamide (0.2 microgram/ml) were effective against Diplozoon paradoxum after an exposure of 90 min and 45 min in vitro. The parasites were severely affected along the midbody. Metrifonate caused a lysis of the tegument and a strong secretion of slime. It is suggested that chemotherapy against Gyrodactylus sp. may be accomplished with 10 mg Praziquantel/l for 3 h during storage in smaller tanks. Niclosamide (0.1 mg/l for 90 min), or Levamisole-HCl (50 mg/l for 120 min) may be used alternatively. Concentrations of Niclosamide and Levamisole-HCl have to be calculated with accuracy, since fish only tolerate a very narrow range of these drugs (Niclosamide: 0.1 mg/l for 120 min; Levamisole-HCl: 50 mg/l for 120 min).

Animals↗
PubMed1996

Levamisole regulates the proliferation of murine liver T cells through Kupffer-cell-derived cytokines.

We have previously shown that levamisole increases the cytotoxic, cytostatic, and proliferative activity of murine nonparenchymal liver cells (NPC) in vitro. We have also shown that the nonadherent subpopulation of NPC, which are composed predominantly of T lymphocytes, is very responsive to this agent when administered to mice. Kupffer cells or immigrant macrophages are also responsive to levamisole but to a lesser extent. These findings prompted us to investigate changes in cytokine production by NPC following-treatment of mice with levamisole (25 mg/kg, i.p.), which may help explain the observed alterations in the immune functions of these cells. We found that levamisole treatment of mice causes a threefold increase in production of interferon (IFN) alpha/beta by adherent NPC (more than 80%-90% Kupffer cells) in vitro. When IFN alpha/beta was added to cultured cells, it decreased the proliferative capacity of liver T cells in a dose-dependent manner. In contrast, the addition of anti-IFN alpha/beta was shown to augment levamisole-induced proliferation of unfractionated NPC and Kupffer cells. NPC production of interleukin 1 (IL-1) and interleukin-6 (IL-6) in vitro was also increased threefold following treatment of mice with levamisole. IL-6 added in vitro to cells significantly augmented levamisole-induced proliferation of liver T cells while anti-IL-6 reduced proliferative activity to control levels. These findings suggested that IFN alpha/beta, IL-6, and IL-1 play important regulatory roles in controlling the proliferative response of murine liver-associated T lymphocytes to levamisole. Finally, the proliferation of bone marrow cells was increased in mice given 5-fluorouracil (5FU). On the other hand, the proliferation of NPC was dramatically suppressed when 5FU was administered. However, the proliferation of these cells was restored when levamisole was given after 5FU.

Adjuvants, Immunologic↗