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PubMed2002

A randomized placebo-controlled trial of mebendazole for halitosis.

OBJECTIVE: To test whether mebendazole, an antiparasitic drug, would affect recovery from halitosis. DESIGN: We conducted a randomized, double-blind, placebo-controlled trial between April 1999 and September 2001. SETTING: A referral medical center. PATIENTS: One hundred sixty-two children aged 5 to 16 years whose parents complained about their chronic bad breath. INTERVENTIONS: Children were randomly assigned to receive mebendazole (n = 82) or placebo (n = 80). MAIN OUTCOME MEASURE: Parents whose children had halitosis were evaluated for halitosis at 2 months of treatment by questionnaire. The microbiologist investigated the stool samples of children for parasitosis at the beginning of the trial and also at the end of the trial in children who were treated with mebendazole. RESULTS: Among those children who had evidence of parasites in stool samples at the beginning of the trial, 18 of 28 who were treated with mebendazole recovered from halitosis, compared with 2 of 24 who received placebo (relative risk [RR] for recovery, 7.7; 95% confidence interval [CI], 2.0-29.9). Among those who did not have stool parasites, 14 of 52 improved with mebendazole, compared with 10 of 48 taking placebo (RR, 1.3; 95% CI, 0.6-2.6). Mebendazole intake made a significant difference whether or not the children had parasites (P =.002). CONCLUSIONS: Parasitosis should be considered as a possible cause of halitosis in the pediatric patient population. Mebendazole therapy seems to offer benefit to those children with parasites as a potential cause of their halitosis.

Adolescent↗
PubMed1983

Chemotherapy of larval echinococcosis with mebendazole: microsomal liver function and cholestasis as determinants of plasma drug level.

High oral doses of mebendazole have been only partly effective in the treatment of patients with alveolar or cystic echinococcosis, possibly due to an inadequate plasma concentration of the drug in some patients. In order to improve therapeutic results the influence of liver function on the plasma levels of mebendazole was investigated during long term therapy. Plasma mebendazole concentrations measured before the morning dose (trough values) showed a highly significant, negative correlation both with the aminopyrine breath test (ABT; rs = -0.78, n = 14, p less than 0.001) and the second exponential component of bromsulphthalein elimination (BSP- k2; rs = -0.74, n = 12, p less than 0.01). These relationships also applied over longer than a single day, since trough and peak mebendazole levels observed over an interval of 6 months before and after testing liver function were equally well correlated with ABT and BSP-k2. The daily dosage and other liver function tests seemed to be of minor importance in determining the plasma levels. It was concluded that the microsomal function of the liver and/or cholestasis might be important determinants of plasma mebendazole levels. The results of the study imply that higher and more effective mebendazole concentrations might be achieved by inhibition of the drug metabolizing capacity of the liver rather than by increasing the dose of mebendazole.

Adult↗
PubMedDate not supplied

4-Amino-3-(3'-methoxycarbonyl-2'-thioureido)benzophenone, a prodrug of mebendazole.

The compound 4-amino-3-(3'-methoxycarbonyl-2'-thioureido) benzophenone has shown promise as a prodrug of the anthelmintic mebendazole. The compound is stable in acid and neutral media and is rapidly hydrolysed in base. An HPLC assay procedure for mebendazole, the prodrug and their known or expected metabolites and degradation products in aqueous media and rat blood has been developed. The prodrug administrated orally to rats is rapidly converted to mebendazole. The area under the blood level versus time curve of mebendazole, in rats dosed with the prodrug, is more than twice that obtained after dosing rats with an equimolar amount of mebendazole. Only the prodrug, mebendazole and known metabolites of mebendazole are detected in rats dosed with the prodrug.

Animals↗
PubMed1983

Efficacy of single doses of mebendazole in the treatment of Trichuris trichiura infection.

Single doses of 100 mg, 200 mg, 400 mg, and 600 mg of mebendazole in the treatment of very light to heavy Trichuris infections all reduced egg output by over 80%. The egg reduction rates were not affected by increased dosages of mebendazole given in heavier infections. Lower cure rates were obtained in patients with heavier worm burdens despite increased dosages of mebendazole, probably as a result of the diarrhea which is frequently associated with heavy Trichuris infection. A single dose of 600 mg mebendazole in the treatment of very light to very heavy infections gave egg reduction and cure rates similar to those obtained with the recommended multiple-dose regime of 100 mg mebendazole twice a day for 3 consecutive days. The single-dose treatment of Trichuris infections with mebendazole is of considerable public health importance as this single dose regime is easy to administer, well-accepted, well tolerated, less expensive, and has a broad spectrum effect. The risk of erratic migration of Ascaris with single doses of mebendazole does not appear to exceed the risk in a multiple-dose regime.

Ascariasis↗
PubMed1981

Chemotherapy of alveolar echinococcosis. Comparison of plasma mebendazole concentrations in animals and man.

High oral doses of mebendazole have been only partly effective in the treatment of patients with alveolar or cystic echinococcosis. In order to improve therapeutic results the pharmacology of mebendazole has been investigated. Jirds experimentally infected with larval Echinococcus multilocularis were given food containing mebendazole 100 to 1000 ppm. Drug plasma concentrations above 0.25 mumol/l were associated with a reduction in parasite weight to 1 to 10% of that in untreated controls. In treated animals parasite weight was negatively correlated with the plasma mebendazole concentration and with the duration of therapy. In patients on long term therapy with similar doses of mebendazole (16 to 48 mg/kg per day), plasma concentrations were much lower than in jirds. Only 19% of fasting plasma concentrations exceeded 0.25 mumol/l. Plasma concentrations 4 h after the morning dose did not exceed this value in 48% of cases. The results can be explained by the irregular drug absorption and short plasma half life observed in 7 hospitalized patients. It is likely that better results would be obtained if doses of mebendazole were adjusted to produce peak plasma levels exceeding 0.25 mumol/l.

Adult↗
PubMed1985

Treatment of cystic echinococcosis (Echinococcus granulosus) with mebendazole: assessment of bound and free drug levels in cyst fluid and of parasite vitality in operative specimens.

Chemotherapy of the larval stage of Echinococcus granulosus in man with high oral doses of mebendazole has only been partly successful. In order to improve effective pharmacotherapy of this disease with mebendazole, the optimal time for blood sampling has been assessed and the mebendazole concentrations acting on the parasite have been compared with their viability. The optimal time for blood sampling was analysed in 14 patients during longterm treatment with mebendazole. The plasma level 4 h after the morning dose exhibited the best correlation with the average 24-h concentration, suggesting that the plasma level should be monitored 4 h after the morning dose. In 22 patients undergoing surgery for hydatid disease, the mebendazole concentration in cyst fluid was significantly correlated with its plasma level 4 h after the morning dose. In 13 of them the free drug concentration was determined by equilibrium dialysis and it was almost identical with the free mebendazole concentration in plasma. Results of viability tests in 12 cases revealed viable cysts in 6 cases and possibly viable cysts in 6 other cases. Even patients treated for more than 12 months still had viable cysts.

Adult↗
PubMed1981

Chemotherapy of onchocerciasis: a controlled comparison of mebendazole, levamisole, and diethylcarbamazine.

Four drug regimens for treating onchocerciasis were compared in a double-blind study in persons from an endemic area in southern Mexico. 40 men were randomly assigned to receive either diethylcarbamazine (DEC) (200 mg/day), mebendazole (2 g/day), levamisole (150 mg per week), or mebendazole plus levamisole. DEC produced the most rapid fall in skin microfilaria counts, but by 6 months the two groups receiving mebendazole showed similar or slightly greater reductions. Despite the administration of corticosteroids to persons receiving DEC, more systemic side-effects were seen in this group. Ocular complications were also commoner and more severe in those receiving DEC. The reduction in the number of intraocular microfilariae at 6 months was similar to those receiving DEC and mebendazole, alone or in combination with levamisole. Levamisole alone had no significant effect on microfilaria counts. Examination of adult worms in nodules excised at 2 months showed changes suggestive of an interruption of embryogenesis in those persons receiving the mebendazole-containing regimens only. The findings suggest that mebendazole may be a useful alternative to DEC in the treatment of onchocerciasis.

Adolescent↗
PubMed2003

Pregnancy outcome after gestational exposure to mebendazole: a prospective controlled cohort study.

OBJECTIVE: Mebendazole is an anthelmintic that is commonly needed in women of reproductive age. Its use in pregnancy is a reason for concern for women and their health care providers. The purpose of this study was to examine the fetal safety of mebendazole. STUDY DESIGN: The Israeli Teratogen Information Service prospectively collected and followed 192 pregnancies exposed to mebendazole in pregnancy, 71.5% of whom had first-trimester exposure. Pregnancy outcome was compared with that of a matched control group, who were counseled for nonteratogenic exposure. RESULTS: There was no increase in the rate of major malformations between the groups (5/150 pregnancies [3.3%; mebendazole] vs 3/175 pregnancies [1.7%; nonteratogenic control subjects]; P =.478). There was a higher rate of elective terminations of pregnancy in the exposed group compared with the control group (22/192 pregnancies [11.5%; mebendazole] vs 3/192 pregnancies [1.6% [nonteratogenic control subjects]; P =.000). CONCLUSION: This study suggests that mebendazole does not represent a major teratogenic risk in humans when it is used in the doses that are used commonly for pinworm (Enterobius vermicularis) infestation.

Abnormalities, Drug-Induced↗
PubMed1985

The effect of dose form on the bioavailability of mebendazole in man.

Four different dose forms of mebendazole were administered to human volunteers, and urine was collected and assayed for mebendazole and unconjugated metabolites of mebendazole. Oral administration of mebendazole as an oily suspension slightly enhances the bioavailability of the drug, however mebendazole is not absorbed following rectal administration. The major urinary metabolite of mebendazole in humans is 2-amino-5(6)[alpha-hydroxybenzyl]benzimidazole (IV), not 2-amino-5(6) benzoylbenzimidazole (II), as previously reported.

Administration, Oral↗
PubMed1987

Cimetidine increases serum mebendazole concentrations. Implications for treatment of hepatic hydatid cysts.

In eight patients (five with peptic ulcer disease and three with hydatid cysts), the [14C]-aminopyrine breath test (ABT) and maximum serum concentration of mebendazole following a dose of 1.5 g of mebendazole three times daily were determined before and after treatment with cimetidine (400 mg three times daily for 30 days). Serum mebendazole concentrations were measured in blood samples taken 2 h after each drug intake. Cimetidine lowered the 14CO2 specific activity (SA) at 1 h (P less than 0.01) and increased the maximum serum concentration of mebendazole (P less than 0.01). A significant correlation was found between SA at 1 h and the highest concentration of mebendazole before (r = -0.71, P less than 0.05) and after (r = -0.82, P less than 0.05) cimetidine ingestion. Combined administration of cimetidine and mebendazole resulted in the complete resolution of previously unresponsive hydatid cysts.

Adult↗
PubMed1978

A clinical trial of mebendazole in the treatment of alveolar hydatid disease.

In July 1974, mebendazole was reported to be effective against the larval stage of Echinococcus granulosus in experimentally infected mice. A clinical trial of mebendazole was initiated in December 1974 in 4 patients with far advanced, nonresectable lesions caused by Echinococcus multilocularis. A daily dose of 40 mg of the drug per kg of body weight was administered to the 4 patients for more than 3 years. No evidence of toxicity or adverse reactions has been observed. Detectable plasma mebendazole concentrations were achieved with high-dose mebendazole therapy. Serum concentrations of IgE increased and decreased early in therapy. There was no evidence that the larval cestode was killed. The metastatic lesions appeared to be stabilized or diminished, and over-all clinical results were encouraging. Progressively enlarging thoracic metastases in 2 patients regressed during therapy, and symptomatic improvement was observed in all 4 patients. Mebendazole, a highly effective antihelmintic in enteric infections, is poorly absorbed by the gastrointestinal tract. Resulting low serum concentrations limit treatment of the massive, scirrhous lesions characteristic of E. multilocularis infections. Nevertheless, encouraging clinical responses observed with mebendazole therapy suggest that a more soluble form of this or a related drug might prove highly effective in the medical management of hydatid disease in humans.

Administration, Oral↗
PubMed1979

Mebendazole.

The broad-spectrum of activity and safety of mebendazole remain, after 5 years of clinical experience, unique features of this anthelmintic. Through microtubular destruction, mebendazole kills helminths by inhibiting glucose uptake into susceptible parasites. The drug's poor absorption does not appear to affect clinical efficacy except, perhaps, in the treatment of systemic helminth infections. Mebendazole is generally considered the drug of choice for trichuriasis and has therapeutic advantages over other anthelmintics in the treatment of enterobiasis and hookworm infections. Although mebendazole is an effective agent against ascariasis, there are preferable alternatives. Among its nonapproved uses, mebendazole shows great promise in the treatment of capillariasis and hydatid disease. Further investigation is needed to establish its role in the treatment of taeniasis, Hymenolepsis nana, strongyloidiasis, trichinosis, and Dipetalonema perstans. Undoubtedly, mebendazole will find its greatest value in the treatment of patients with multiple helminth infections.

Ascariasis↗
PubMed1992

[Long-term therapy of cystic liver echinococcosis with mebendazole].

Surgery is the therapy of choice in the treatment of infestations with Echinococcus (E.) granulosus and E. multilocularis. Chemotherapy with mebendazole, a benzimidazole derivative, introduced 1976 in the therapy of human echinococcosis, showed good results only in cases of infestation with E. multilocularis. In the cases of liver cysts, caused by E. granulosus, the treatment with mebendazole did not succeed as well. Between 1977 and 1986, 44 patients, suffering from infestations with E. granulosus, were referred to the Clinical Department of the Bernhard-Nocht-Institut. In a retrospective study, the data of seven patients had been evaluated: They had not undergone surgery because of the size of the lesions or because they refused the operative treatment. Receiving mebendazole as the only therapy, they had been treated and followed up for more than four years. Mebendazole was given in a dosage of 50 mg/kg body weight in repeated cycles of one month's duration followed by a treatment-free interval of two months. After a median of 55 months (median 13 effective treatment months) six of the seven patients presented a therapeutical success as demonstrated by ultrasound and computed tomography. The cystic lesions had dissolved or decreased in size considerably. One case showed unaltered findings of the liver lesion. Mebendazole treatment was well tolerated by all patients. If the size of the cystic liver-lesions excludes a curative operative treatment or if the patient refuses surgery, the indication for chemotherapy with mebendazole is given.

Adult↗
PubMed1992

Brugia malayi in Mastomys natalensis: efficacy of mebendazole in combination with Freund's complete adjuvant.

The chemotherapeutic efficacy of mebendazole given in combination with Freund's complete adjuvant (FCA) against Brugia malayi in multimammate rat was evaluated. Animals treated with mebendazole, orally at 200 mg/kg x 5 consecutive days along with FCA given subcutaneously (s.c.) on day -10, day 0 and day +15 of the drug treatment killed 48.51% of the adult worms. This drug given alone at the same regimen and by the same route showed only 18.7% mortality rate on adults. Mebendazole given intraperitoneally along with FCA given s.c., however, was four times more efficacious as filaricide than mebendazole alone. Nevertheless, the animals receiving FCA alone also revealed 23.5% mortality rate of adult worms. The animals receiving a combination therapy or FCA alone showed significant increase in antibody titre to the filariae which however decreased in the later stages. No enhancement of antibody level could be detected in animals treated with mebendazole alone. The non-specific immunopotentiation induced by FCA appeared to play a major role in enhancing the activity of mebendazole.

Administration, Oral↗
PubMed1984

The effects of diethylcarbamazine, mebendazole and levamisole on Onchocerca volvulus in vivo and in vitro.

The effects of mebendazole, levamisole, diethylcarbamazine citrate (DEC-C), and the combination of mebendazole and levamisole, on adult Onchocerca volvulus and on the in utero development of microfilariae was studied in nodules excised from patients in Southern Mexico. Adult worms isolated from patients treated with mebendazole showed a reduction in mobility and contained 40 times fewer developing microfilarial forms than did worms from untreated patients. Most of the developmental forms found in adult worms from mebendazole-treated patients were either oocytes or early morulae, with more mature forms being scarce or morphologically abnormal. Treatment with levamisole had a similar effect on embryogenesis, however it was much less marked. The number and distribution of developing forms in worms from patients treated with DEC-C was similar to that found in the control groups. The effect of the same three drugs on microfilariae in vitro was also tested. DEC-C at concentrations of 0.5 microgram - 2000 micrograms/ml did not have any obvious effect on motility or morphology of the worms provided the pH was maintained at physiological levels; levamisole also had no effect in vitro. Mebendazole induced the death of microfilariae when used at concentrations greater than 100 micrograms/ml, however these levels are greater than those found in the blood of patients under treatment. The optimal conditions for short-term maintenance of O. volvulus microfilariae in culture, are discussed. It is apparent from these studies that mebendazole has an effect on the maturation of microfilariae in utero and may also, at high concentrations, have a direct effect on mature microfilariae.

Animals↗
PubMed1984

Improvement of metabolic control in diabetic patients during mebendazole administration: preliminary studies.

After the observation of decreasing insulin resistance in a diabetic patient during treatment with mebendazole for nematosis, we investigated the effect of mebendazole on metabolic control in six Type 1 (insulin-dependent) and six Type 2 (non-insulin-dependent) diabetic patients, eight of whom were chronically resistant to conventional treatment. Before and after mebendazole treatment for 1 month, plasma glucose and serum C-peptide concentrations were determined both fasting and 4 h after a mixed breakfast. Improvements in fasting blood glucose concentrations occurred in Type 1 (12.83 +/- 1.11 versus 6.56 +/- 0.56 mmol/l; p less than 0.05) and Type 2 (10.22 +/- 0.56 versus 7.56 +/- 0.67 mmol/l; p less than 0.05) diabetic patients and were associated with increases in post-cibal C-peptide responses in Type 1 and Type 2 diabetic patients. Following discontinuation of mebendazole, metabolic control deteriorated in five out of the six Type 1 diabetic patients and in all the Type 2 diabetic patients. We conclude that mebendazole increases insulin secretion, and decreases plasma glucose concentration in Type 1 and Type 2 diabetic patients. However, these beneficial effects may be transient.

Adult↗
PubMedDate not supplied

The metabolic and pharmacokinetic disposition of mebendazole in the rat.

The metabolism and pharmacokinetics of mebendazole was studied in rats using [2'-3H]-mebendazole (biologically stable; specific activity 383.9 (mCi/mMol) and [2-14C]-mebendazole (specific activity 2.57 mCi/mMol). Analyses were performed by high pressure liquid chromatography and liquid scintillation spectrometry. About 85% of an intravenous dose was eliminated with the bile and the remainder with the urine. The majority of the dose was recovered as conjugated metabolites. The major metabolite (methyl-5(6)-(alpha-hydroxybenzyl)-2-benzimidazole carbamate) accounted for about 77% of the total recovered and 99% of it was conjugated. Anaerobic metabolism studies conducted in vitro with intestinal microorganisms obtained from rats indicated that metabolism of mebendazole did not occur in the gut, but that the intestinal microflora was able to hydrolyse conjugated metabolites which were eliminated with the bile. Mebendazole was found to have a biphasic elimination profile after intravenous administration. Its terminal plasma elimination half-life was 3.2 hours and its re-distribution half-life was 0.4 hour. After oral administration, as a solution in aqueous dimethyl sulphoxide, a bioavailability of 53% was obtained.

Administration, Oral↗
PubMed1996

Effects of mebendazole on protein biosynthesis and secretion in human-derived fibroblast cultures.

Previous results of our group revealed that mebendazole, a broad spectrum anthelmintic drug with antimicrotubular properties, used for the treatment of liver cirrhosis, decreased total collagen content and biosynthesis in liver upon treatment. In the present study, we have evaluated the effects of mebendazole (5-50 micrograms/mL) on protein synthesis, secretion, and deposition in human-derived fibroblast cultures. The results showed a decrease in cell viability (18.5 +/- 0.9%) at 50 micrograms/mL. [3H]Thymidine incorporation diminished gradually with increasing mebendazole concentrations, reaching a plateau (53.67%) between 30 and 50 micrograms/mL. In late logarithmic phase cultures, the drug caused a decrease of [3H]proline incorporation (43.10%) and collagen biosynthesis (58.61%) in the extracellular matrix. This correlated with an increase in radioactivity in total proteins (51.28%) of the intracellular fraction. Similar results were obtained when mebendazole was assayed in post-confluent fibroblast cultures. The electrophoretic patterns of the extracellular matrix showed a decrease of radioactive collagenous components (alpha chains and beta dimers). By contrast, in the intracellular fraction an increase of radioactive collagen precursors (pro alpha chains) was observed. Immunofluorescence studies and immunotransfer analysis, using polyclonal anti-type I collagen antibodies, revealed an accumulation of intracellular collagen which included: collagen pro alpha chains, alpha chains, and low molecular weight peptides. The results obtained suggest that mebendazole interferes with the transcellular mobilization of proteins, resulting in a decrease of secretion and deposition of extracellular matrix proteins, and an accumulation of intracellular collagenous components. The intracellular accumulation of newly synthesized proteins could cause a feedback regulation in fibroblast cultures.

Antinematodal Agents↗