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At least 19 recordsLinked to original sources
PubMed1980

In vitro activities of miconazole, miconazole nitrate, and ketoconazole alone and combined with rifampin against Candida spp. and Torulopsis glabrata recovered from cancer patients.

A total of 440 fresh clinical isolates of yeasts from cancer patients were tested by an agar dilution technique against miconazole, miconazole nitrate, and ketoconazole individually and combined with 5 micrograms of rifampin per ml. Most strains of Candida albicans were susceptible to 0.5 microgram or less of the imidazoles per ml. Candida tropicalis required 2 to 4 micrograms of miconazole and its nitrate base per ml for inhibition and was resistant to ketoconazole. The 100% minimal inhibitory concentration of the imidazoles for Candida krusei was 1 microgram/ml. Susceptibility to 4 micrograms of miconazole and miconazole nitrate per ml occurred in 73 and 87% of Torulopsis glabrata strains, respectively, and none was susceptible to ketoconazole. Miconazole was most effective against the Candida spp., whereas its nitrate base was most active against T. glabrata. Synergy was observed when rifampin was combined with miconazole and miconazole nitrate but was not observed when rifampin was combined with ketoconazole. Synergy occurred most frequently when rifampin was combined with miconazole nitrate.

Antifungal Agents↗
PubMed1986

Seborrhoeic dermatitis and Pityrosporum orbiculare: treatment of seborrhoeic dermatitis of the scalp with miconazole-hydrocortisone (Daktacort), miconazole and hydrocortisone.

Seventy patients (36 males and 34 females) with seborrhoeic dermatitis of the scalp were treated in a double-blind controlled study, for a maximum of 6 weeks, with 2% miconazole base and 1% hydrocortisone (Daktacort), 2% miconazole base, or 1% hydrocortisone. Patients who were cured were treated with the same formulation prophylactically twice monthly for 3 months or until recurrence. Nineteen of 21 patients were cured in the Daktacort group, 15 of 22 in the miconazole group and 17 of 24 in the hydrocortisone group. The number of cultured Pityrosporum orbiculare was significantly lower in all groups after treatment, but in the hydrocortisone group was still significantly higher than in the two other groups. After 3 months of prophylactic treatment, both Daktacort (16 of 19 patients clear) and miconazole (10 of 15 patients clear) were significantly better than hydrocortisone (3 of 17 patients clear) (P less than 0.01). The numbers of P. orbiculare remained low in the Daktacort and miconazole groups and also significantly lower than in the hydrocortisone-treated group (P less than 0.01). In patients with recurrence, the numbers returned to pre-treatment levels. This study demonstrates the aetiological significance of the Pityrosporum yeasts in seborrhoeic dermatitis. Both Daktacort and miconazole were effective in treatment and as prophylactic agents.

Adult↗
PubMed1976

Mechanism of action of miconazole: labilization of rat liver lysosomes in vitro by miconazole.

Miconazole, a potent antifungal agent, labilizes rat liver lysosomes. Its labilizing effect is followed by measuring the release of lysosomal hydrolases, namely, acid phosphatase, beta-glucuronidase, and arylsulfatase A. The effect of miconazole is concentration dependent in the range of 10(-5) to 1.2 x 10(-4) M. However, at higher concentrations, miconazole inhibits enzyme release but does not inhibit enzyme activities per se. The effect of miconazole depends on the drug/lysosome ratio and is influenced by the pH of the incubation media, being minimal at alkaline pH. Membrane-active drugs such as nystatin, 2-phenethyl-alcohol, hexachlorophene, and digitonin have been compared with miconazole for their lysosome-labilizing action. The effect of miconazole on the lysosomal membrane is confirmed by a decrease in turbidity of the lysosomal suspension.

Acid Phosphatase↗
PubMed2000

Single-dose miconazole nitrate vaginal ovule in the treatment of vulvovaginal candidiasis: two single-blind, controlled studies versus miconazole nitrate 100 mg cream for 7 days.

To determine the efficacy and safety of a single-dose (1200 mg) soft gel insert (vaginal ovule) with miconazole nitrate (2%) topical cream compared with Monistat 7 (miconazole nitrate 2%) Vaginal Cream (Advanced Care Products, North Brunswick NJ) in treating vulvovaginal candidiasis (VVC), two randomized, single-blind, multicenter, controlled, comparative phase III studies were performed. Five hundred fifty-eight patients received either a single-dose miconazole nitrate (1200 mg) ovule or seven consecutive doses of Monistat 7. Ovule arm patients also received miconazole nitrate 2% cream for symptom relief, as needed, up to twice daily. The primary end point was a therapeutic cure. Also evaluated were time to complete symptom relief, safety, and patient preference. The ovule had overall cure rates of 71.7% (71 of 99 patients) and 61.5% (64 of 104 patients). Monistat 7 had overall cure rates of 70.1% (68 of 97 patients) and 61.1% (55 of 90 patients). A significantly greater proportion of patients experienced complete symptom relief by day 3 with the ovule (p = 0.008 and p = 0.025), and time to complete relief was significantly faster (median 4 versus 5 days and 3 versus 4 days). Overall safety results were consistent between groups in both studies. Miconazole nitrate vaginal ovule is as safe and efficacious in curing VVC as Monistat 7 while providing complete symptom relief significantly faster. Patients preferred the ovule to prior therapy.

Administration, Intravaginal↗
PubMedDate not supplied

Resistance of Candida albicans to direct lethal miconazole action induced by low-level miconazole.

Logarithmic phase cells of Candida albicans are susceptible to physicochemical damage by greater than or equal to 2 x 10(-5)mol miconazole resulting in direct lethal action (DLA). Stationary phase yeasts are resistant to such action. At low levels (i.e. less than 10(-5)mol), miconazole can inhibit synthesis of cell membrane components and can also revert DLA-susceptible cells to DLA resistance. Reversion was studied in relation to low-level miconazole exposure time. DLA was assessed by viable count determinations. Most cells in susceptible cultures reverted to resistance within 30 to 60 min of exposure to 2.0 x 10(-6)mol miconazole. The rapidity of this shift suggested subtle alterations in existing cell membrane material in response to low-level miconazole. Saturation of membrane fatty acids might explain the shift.

Candida albicans↗
PubMed1988

Antagonism of the direct fungicidal action of miconazole by miconazole fungistasis.

A weakly fungistatic concentration of miconazole in lag phase yeast cultures of Candida albicans antagonized development of phenotypic susceptibility to the direct fungicidal action of high-level (i.e. greater than 10(-5) M) miconazole. After development in the absence of drug, maintenance of susceptibility upon continued incubation was also antagonized by low levels of miconazole. This auto-antagonistic effect has important clinical implications.

Candida albicans↗
PubMed2001

In vitro comparison of the antimycotic activity of a miconazole-HP-beta-cyclodextrin solution with a miconazole surfactant solution.

The antimycotic activity of a new parenteral solution containing miconazole was compared with that of a marketed solution (Daktarin IV solution). This solution has been withdrawn from the Belgian market, probably because of toxic effects related to the presence of polyoxyl 35 castor oil. We propose a new formulation containing miconazole (10 mg/mL) (like the marketed solution), in combination with hydroxypropyl-beta-cyclodextrin and lactic acid. The MICs of these two solutions were determined by a broth microdilution method (based on NCCLS guidelines) for 67 yeasts and 50 filamentous fungi isolates. This study shows that the MICs obtained with these two solutions are not significantly different.

2-Hydroxypropyl-beta-cyclodextrin↗
PubMed1999

Mechanisms of miconazole-induced rise in cytoplasmic calcium concentrations in Madin Darby canine kidney (MDCK) cells.

The effect of miconazole on intracellular calcium levels ([Ca2+]i) in Madin Darby canine kidney (MDCK) cells was studied using fura-2 as the Ca2+ indicator. Miconazole increased [Ca2+]i dose-dependently at concentrations of 5-100 microM. The [Ca2+]i transient consisted of an initial rise, a gradual decay and an elevated plateau (220 s after addition of the drug). Removal of extracellular Ca2+ partly reduced the miconazole response. Mn2+ quench of fura-2 fluorescence confirmed that miconazole induced Ca2+ influx. The miconazole-sensitive intracellular Ca2+ store overlapped with that sensitive to thapsigargin, an inhibitor of the endoplasmic reticulum Ca2+ pump, because 20 microM miconazole depleted the thapsigargin (1 microM)-sensitive store, and conversely, thapsigargin abolished miconazole-induced internal Ca2+ release. Miconazole (20-50 microM) partly inhibited the capacitative Ca2+ entry induced by 1 microM thapsigargin, measured by depleting intracellular Ca2+ store in Ca(2+)-free medium followed by addition of 10 mM CaCl2. Miconazole induced capacitative Ca2+ entry on its own. Pretreatment with 0.1 mM La3+ partly inhibited 20 microM miconazole-induced Mn2+ quench of fura-2 fluorescence and [Ca2+]i rise, suggesting that miconazole induced Ca2+ influx via two pathways separable by 0.1 mM La3+. Miconazole-induced internal Ca2+ release was not altered when the cytosolic level of inositol 1,4,5-trisphosphate (IP3) was substantially inhibited by the phospholipase C inhibitor U73122.

Animals↗
PubMed1997

Treatment of oropharyngeal candidiasis in immunocompetent infants: a randomized multicenter study of miconazole gel vs. nystatin suspension. The Antifungals Study Group.

BACKGROUND: Miconazole gel has previously been shown to be an effective treatment for oropharyngeal candidiasis (thrush) in immunocompetent infants. This study compares miconazole gel with the standard therapeutic agent, nystatin suspension, with regard to efficacy, optimal duration of therapy and safety. DESIGN: Prospective multicenter, randomized, office-based open trial. PATIENTS: Twenty-six pediatricians enrolled 227 immunocompetent infants with signs of oropharyngeal thrush. Subjects were randomly assigned to receive 25 mg of miconazole as oral gel four times daily or 100,000 IU of nystatin as suspension four times daily after meals. All subjects were evaluated for safety. Fifteen patients whose thrush was not confirmed by culture were excluded from further analysis. The remaining 212 subjects were entered into an intention-to-treat analysis. Another 29 patients violated the study protocol; the remaining 183 subjects were evaluated for efficacy (per protocol analysis). RESULTS: Clinical cure by Day 5 of treatment was demonstrated in 84.7% of the 98 subjects in the miconazole group and 21.2% of the 85 subjects in the nystatin group (P < 0.0001). By Day 8, the cumulative clinical cure rates were 96.9% (miconazole) and 37.6% (nystatin), respectively (P < 0.0001). By Day 12.99.0% of subjects in the miconazole group and 54.1% of subjects in the nystatin group were clinically cured (P < 0.0001). Premature cessation of treatment at parents' request because of lack of clinical efficacy occurred in none of the infants treated with miconazole and in 6 infants treated with nystatin (P = 0.029). The oral yeast eradication rate on Day 5 was 54.1% with miconazole and 8.2% with nystatin (P < 0.0001). Clinical relapses of oropharyngeal thrush and side effects of the study drugs were observed with similar frequency in both study arms. CONCLUSIONS: Miconazole gel was significantly superior to nystatin suspension with regard to efficacy, rapidity of achieving cure and oropharyngeal yeast eradication. Relapses and side effects did not occur more frequently with miconazole than with nystatin. The results of this study indicate that miconazole gel is superior to nystatin suspension as the treatment for oropharyngeal candidiasis in immunocompetent infants.

Antifungal Agents↗
PubMed1978

Treatment of experimental murine cryptococcosis: a comparison of miconazole and amphotericin B.

Miconazole was compared with amphotericin B in the treatment of murine cryptococcosis. Both subcutaneous and intraperitoneal administration of miconazole produced serum levels higher than the minimum inhibitory concentration for the challenge strain. However, maximal tolerable doses of miconazole gave no increase in survival. When combined with amphotericin B, miconazole demonstrated neither additive nor antagonistic effects on survival. Spleen and brain counts of cryptococci were not lowered by miconazole; also, miconazole did not alter the effect of amphotericin B on reducing tissue counts. In vitro studies confirmed that the strain of Cryptococcus neoformans was quite susceptible to both miconazole and amphotericin B. However, miconazole had a delayed onset of antifungal activity. This was apparent even at miconazole levels 20 times greater than the minimum inhibitory concentration. Also, the antifungal activity of miconazole was markedly inhibited by serum. Delayed antifungal activity and serum inhibition may limit the in vivo effectiveness of miconazole in murine cryptococcosis.

Amphotericin B↗
PubMedDate not supplied

Effect of miconazole on warfarin disposition in rabbits.

To elucidate the mechanism underlying the reported potentiation of warfarin anticoagulant action after initiation of miconazole therapy, the effects of acute and chronic miconazole administration on warfarin disposition were examined in six adult New Zealand male rabbits. The rabbits received a 3.5 mg/kg iv dose of warfarin either alone, 1 hr after a single 100 mg/kg ip miconazole dose, or on day 5 of a 6-day 50 mg/kg/12 hr ip miconazole dosing regimen. Acute miconazole administration decreased the elimination rate constant of warfarin, but other warfarin disposition parameters were not altered. Chronic miconazole administration caused a 47% increase in warfarin plasma-free fraction (probably caused by competitive or noncompetitive protein binding displacement by miconazole metabolites) and a 42% decrease in warfarin intrinsic clearance (probably caused by a miconazole-induced inhibition in warfarin metabolism). As a consequence of these quantitatively similar but opposite changes, the total body clearance of warfarin (a low clearance drug) was marginally decreased. A significant decrease in the elimination rate constant and an increase in the tissue-free fraction of warfarin were also observed during chronic miconazole treatment. These results suggest that chronic miconazole administration should not significantly affect the steady-state plasma concentrations of total warfarin, but should increase the steady-state plasma concentrations of free warfarin. The expected increases in the steady-state plasma concentrations of free, pharmacologically active warfarin may account for the reported potentiation of the pharmacological action of warfarin when coadministered with chronic miconazole. Measurement of total plasma concentrations, and estimation of total body clearance might be misleading, and inadequate in identifying certain drug interactions involving low clearance drugs.

Animals↗
PubMed1986

Miconazole inhibition of platelet aggregation by inhibiting cyclooxygenase.

Platelet dysfunction was found in rabbits to which a dose of miconazole nitrate (1.6 mg/kg body wt) therapeutic for human subjects had been given intravenously. The present experiments were conducted to elucidate the mechanism of inhibitory effects of miconazole on platelet function. After administration of a single dose of miconazole, rabbit platelet aggregation induced by collagen and sodium arachidonate was inhibited significantly for approximately 24 hr. On the other hand, hypertriglycemia, one of the major side effects of this drug, was not seen during 2 days of observations, nor were any other outstanding manifestations observed. In in vitro experiments, miconazole nitrate (10 microM) also significantly inhibited rabbit and human platelet aggregation (P less than 0.01). Biochemical analyses revealed that the stimulant-induced formation of prostaglandin E2 (PGE2) and thromboxane B2 (TXB2), metabolites via cyclooxygenase, was inhibited by miconazole nitrate in both human and rabbit platelets in vitro. PGE2 production was decreased dose-dependently with the increase of miconazole concentration (10 to 100 microM), and the decrease was in parallel with a decrease of TXB2 production. In addition, malondialdehyde (MDA) production of human and rabbit platelets induced by exogenous arachidonate and collagen was also inhibited significantly by miconazole. Chromatographic studies showed that the amount of 12-L-hydroxy-5,8,10,14-eicosatetraenoic acid (HETE), a metabolite via lipoxygenase, was increased markedly in accordance with the miconazole-induced decrease of TXB2 and 12-L-hydroxy-5,8,10-heptadecatrienoic acid (HHT) formation in both human and rabbit platelets. These results indicate that miconazole nitrate inhibits platelet cyclooxygenase, without affecting the stimulant-induced release of arachidonic acid from platelet phospholipids. Use of this drug in the treatment of systemic fungal infection appears to be increasing. Careful attention should be paid to the inhibitory effects of miconazole on platelet function, especially in the case of intravenous treatment.

Adenosine Diphosphate↗
PubMed1986

Induction potential of antifungals containing an imidazole or triazole moiety. Miconazole and ketoconazole, but not itraconazole are able to induce hepatic drug metabolizing enzymes of male rats at high doses.

Male Wistar rats were dosed with miconazole, ketoconazole and itraconazole by gastric intubation once daily for up to 7 days. A dose- and time-dependent induction of the hepatic drug metabolizing enzyme system was observed for miconazole and ketoconazole, while itraconazole proved to be devoid of inductive properties even at the highest dose studied (160 mg/kg). No effect on drug metabolizing enzymes could be demonstrated for either drug at a dose level of 10 mg/kg, which is just above the antifungally active dose. At a dose of 40 mg/kg, miconazole, but not ketoconazole, significantly increased cytochrome P-450 content. At the highest dose of 160 mg/kg, both miconazole and ketoconazole increased the relative liver weight, the cytochrome P-450- and b5-content and NADPH-cyt c-reductase. Furthermore, miconazole, but not ketoconazole, increased specific microsomal aminopyrine and N,N-dimethylaniline N-demethylase activity, p-nitroanisole O-demethylase activity and UDP-glucuronyltransferase activity towards 4-nitrophenol while the specific aniline hydroxylase activity was unaffected. Ketoconazole at 160 mg/kg only induced O-demethylase activity and UDP-glucuronyltransferase activity, while it lowered the specific activities towards the other substrates. Miconazole was a relatively more potent inducer when compared to ketoconazole. Both drugs displayed biphasic effects on the mixed-function oxidase activities, which were lowered after acute administration (160 mg/kg, 1 hr before death) and were induced when determined after 23 hr had elapsed or after multiple dosage. Both drugs bound strongly to their respective induced cytochromes, giving rise to type II difference spectra, and inhibited the O-demethylase activity of the induced microsomes with an I50 of 5.2 microM for miconazole and 15.1 microM for ketoconazole. On the basis of a comparison of the enzymatic activities induced by both antimycotics with those induced by PB or 3-MC, it was concluded that miconazole behaved as a PB-type inducer, whereas ketoconazole did not belong to either category of inducers. A comparison of electrophoretograms of microsomes from different origins on SDS-PAGE revealed that miconazole increased the concentration of several proteins, whereas ketoconazole selectively induced a protein with Mr of 47,800. The protein pattern in the 50 kDa region of miconazole-induced microsomes resembled that of PB-microsomes qualitatively.

Aniline Hydroxylase↗
PubMed1995

Stability, compatibility and plasticizer extraction of miconazole injection added to infusion solutions and stored in PVC containers.

The stability of miconazole in various diluents and polyvinyl chloride (PVC) containers was determined and the release of diethylhexyl phthalate (DEHP) from PVC bags into intravenous infusions of miconazole was measured. An injection formulation (80 ml) containing a 1% solution of miconazole with 11.5% of Cremophor EL was added to 250-ml PVC infusion bags containing 5% glucose injection or 0.9% sodium chloride injection, to give an initial nominal miconazole concentration of 2.42 mg ml-1, the mean concentration commonly used in clinical practice. Samples were assayed by stability-indicating high-performance liquid chromatography (HPLC) and the clarity was determined visually. Experiments were conducted to determine whether the stability and compatibility of miconazole would be compromised, and whether DEHP would be leached from PVC bags and PVC administration sets during storage and simulated infusion. There was no substantial loss of miconazole over 2 h simulated infusion irrespective of the diluent, and over 24 h storage irrespective of temperature (2-6 degrees C and 22-26 degrees C). All the solutions initially appeared slightly hazy. Leaching of DEHP was also detected during simulated delivery using PVC bags and PVC administration sets. There was a substantial difference between the amounts of DEHP released from PVC bags and from administration sets, and also between the amounts released in solutions stored in PVC bags at 2-6 degrees C and 22-26 degrees C over 24 h. At the dilution studied, miconazole was visually and chemically stable for up to 24 h. The storage of miconazole solutions in PVC bags seems to be limited by the leaching of DEHP rather than by degradation. To minimize patient exposure to DEHP, miconazole solutions should be infused immediately after their preparation in PVC bags.

Antifungal Agents↗
PubMed1999

Cyclodextrin inclusion complexes of miconazole and econazole--isolation, toxicity on human cells, and confirmation of a new interpretation of the drug supersaturation phenomenon.

Parameters that influence the precipitation of the beta-cyclodextrin (beta-CD) inclusion complexes of the antimycotics miconazole and econazole were investigated. The mechanistic reason for the superior antimycotic activity of the miconazole inclusion complex was studied. The toxicity of the complex was estimated. The temperature, the buffer strength, and the effect of the addition of hydrotropic agents on the CD solubility diagrams for the antimycotics were estimated. The miconazole and the CD dissolution rate for the complex was measured. The hemolytic activity of the miconazole inclusion complex, the physical mixture, miconazole, and the nitrate salt were compared. The toxicity on TR146 oral cell layers was measured. Lowering the temperature meant that both complexes precipitated at lower CD concentrations. Addition of hydrotropic agents and variation of the buffer strength affected the solubility diagrams. The dissolution medium was supersaturated with miconazole. The supersaturation was not disclosed by the traditional method to analyze for drug supersaturation. The miconazole complex was more toxic to erythrocytes than the physical mixture. On the other hand, the toxic effects of the two products on the TR146 cell layers were similar. Lowering the temperature eased the isolation of genuine CD inclusion complexes of miconazole and econazole. The miconazole supersaturation is likely to be the reason for the superior antimycotic activity of the complex. The complex and the physical mixture had about the same toxicity on TR146 cell layers.

Antifungal Agents↗
PubMed1978

Therapeutic failures with miconazole.

A retrospective review of therapeutic failures of miconazole in three patients is presented. Miconazole, a new imidazole derivative, is a broad-spectrum antifungal agent purportedly effective topically, orally, and parenterally against a number of species of fungi. Three patients with the following culturally proven deep fungal infections were treated with miconazole: (i) destructive arthritis (Sporothrix schenckii), (ii) meningoencephalitis (Cryptococcus neoformans), and (iii) disseminated aspergillosis (Aspergillus fumigatus). All the organisms were susceptible in vitro to 1.56 mug or less of miconazole per ml using a broth dilution technique. In each patient, miconazole administered intravenously in dosages of 30 mg/kg per day failed to control or eradicate infection. Miconazole serum levels ranged from <0.5 to 4.35 mug/ml as determined by radial diffusion bioassay. Cerebrospinal fluid levels were virtually undetectable. In one patient (C. neoformans), miconazole was given intraventricularly in doses of 15 mg without response. Therapeutic failures were attributed to suboptimal body fluid levels of miconazole. The reason(s) for such low levels of activity was not clear, but may have been poor penetrance into tissues, in vitro inactivation, and/or unusually rapid excretion. Untoward reactions from miconazole included fever, chills, nausea, vomiting, and phlebitis.

Adult↗