Disease relevance of miconazole

• Disseminated candidiasis in a patient with acute leukemia. Successful treatment with miconazole [1].
• Treatment of coccidioidomycosis with miconazole [2].
• Miconazole in paracoccidioidomycosis [3].
• Miconazole in fungal endophthalmitis [4].
• Cardiorespiratory toxicity due to miconazole [5].

Psychiatry related information on miconazole

• The anomalous response to subconjunctival therapy with miconazole seen in this model suggests an effect on host defense mechanisms [6].
• Patient compliance was acceptable according to regular miconazole determination in saliva samples [7].
• Daily mouthwashes with 0.12% chlorhexidine and application of miconazole gel were added to the therapy; its response time to treatment varied individually, the doses were reduced only after 75% of lesions had cleared [8].

High impact information on miconazole

• Case reports and studies involving antifungals such as amphotericin B bladder irrigation, miconazole nitrate bladder irrigation, ketoconazole, and flucytosine were reviewed [9].
• Extensive in vivo and in vitro immunological studies done before and after successful treatment with miconazole showed a persistent partial deficiency of the cell-mediated immune system, in particular that directed toward candida antigens [10].
• Miconazole in cryptococcosis and systemic candidiasis: a word of caution [11].
• Successful treatment of cerebral cryptococcoma and meningitis with miconazole [12].
• Seven patients with hematologic malignancies who were treated with miconazole for either suspected or proven fungal infections developed eight episodes of major adverse cardiorespiratory and anaphylactic reactions [5].

Chemical compound and disease context of miconazole

• In this regard, haloperidol, a non-phenothiazine calmodulin antagonist, and R24571, a derivative of the antimycotic miconazole, which is a potent and highly specific calmodulin inhibitor, also blocked EBV infection [13].
• In view of recent evidence that the imidazole antifungals econazole (EC) and miconazole (MC) inhibit TG-sensitive Ca(2+)-ATPase activity in normal rat thymocytes, we investigated the effect of these agents on intracellular Ca(2+) homeostasis and cell survival in WEHI7.2 mouse lymphoma cells and human CEMT-cell leukemia cells [14].
• Two patients survived their infections, which included involvement of other body sites (lung, eye, bone) as well as multiple undrained brain abscesses, after prolonged courses of high-dose parenteral miconazole (80-90 mg/kg/d) [15].
• Toxicity of amphotericin B, miconazole, and ketoconazole to human granulocyte progenitor cells in vitro [16].
• Guinea pigs were infected intravaginally with HSV-2 and treated both intravaginally and topically on the external genitalia four times a day with 1% or 5% 2-DG in miconazole nitrate cream [17].

Biological context of miconazole

• Imidazole antifungals Miconazole and Econazole induce apoptosis in mouse lymphoma and human T cell leukemia cells: regulation by Bcl-2 and potential role of calcium [14].
• IC50 values were (in microM): clotrimazole, 0.05; tioconazole, 0.3; miconazole, 1.5; econazole, 1 [18].
• Inhibition of warfarin hydroxylation by miconazole in human liver microsomes and the in vivo results showed a good rank order correlation [19].
• In vivo pharmacokinetics and pharmacodynamics of topical ketoconazole and miconazole in human stratum corneum [20].
• There are several other drugs which enhance the hypoprothrombinaemic response to coumarins by various mechanisms: inhibitors of the elimination of the eutomer S-(-)-warfarin (e.g. miconazole, phenylbutazone), combined with protein binding displacement (e.g., sulfinpyrazone, phenylbutazone), synergistic hypoprothrombinaemia (e.g. cefazoline) [21].

Anatomical context of miconazole

• Methacholine also caused hyperpolarization of coronary smooth muscle (-27 +/- 3.9 versus -40 +/- 5.1 mV), which was completely blocked by SKF 525A and miconazole [22].
• The microsomal reaction is inhibited by 3-methylcholanthrene, miconazole, or 7,8-benzoflavone, 7-Iodo-2-acetylaminofluorene is N-hydroxylated by guinea pig liver microsomes at approximately the same rate as 2-acetylaminofluorene [23].
• By contrast, the differential effect of miconazole on 3Y1 and AD-12-transformed cell lines was found to be a factor of 2 [24].
• RESULTS: Based on elution time of known standards and inhibition by miconazole, an inhibitor of P450 AA epoxygenase, cultured astrocytes produce 11,12- and 14,15-EETs when incubated with AA [25].
• The response of laser-Doppler cerebral blood flow to administration of glutamate (500 mumol/L) into the subdural space of the rat was significantly attenuated after treatment with miconazole (20 mumol/L for 30 minutes) [26].

Associations of miconazole with other chemical compounds

• Both 17-ODYA and miconazole (10(-5) mol/L, a chemically distinct P450 inhibitor) further reduced the dilation to AA in the presence of INDO [27].
• Clotrimazole and miconazole were also strong inhibitors of P450 3A-mediated activities in contrast to the other imidazole derivatives [28].
• The transcription rates of mEH mRNA at 24 hr were significantly less than those observed at 12 hr after a single treatment with either ketoconazole, miconazole, or econazole, resulting in 6.5-, 2.5-, and 2-fold increases, respectively, relative to control [29].
• In the current study, we investigated the effect of ketoconazole and other azole-derived drugs, miconazole and fluconazole, on the transcriptional activity of the human GR (hGR) in HeLa and HepG2 cells, and in primary human hepatocytes [30].
• RESULTS: Glutamate treatment (100 mumol/L for 30 minutes) induced a threefold increase in the formation of EETs from [14C]AA by cultured astrocytes, and the increase was inhibited by miconazole (20 mumol/L), an inhibitor of P-450 AA epoxygenase [26].
• In rat liver microsomes in vitro, defluorination of 18F-FCWAY was almost completely inhibited by miconazole and, to a less extent, by diclofenac [31].
• With respect to the antifungal activity of miconazole, we demonstrate an antagonism with tryptophan and a synergy with a yeast endocytosis inhibitor [32].

Gene context of miconazole

• Fluconazole, miconazole and sulfamethoxazole are potent inhibitors of CYP2C9 [33].
• The formation of FLU-1-N-OH was markedly inhibited by the addition of miconazole, an inhibitor of CYP3A4, and was mediated by recombinant CYP3A4 [34].
• The MDR1-mediated transport of [3H]digoxin was inhibited by ketoconazole and itraconazole, and slightly by miconazole [35].
• These results suggest that miconazole is the strongest inhibitor against CYP1A2, CYP2D6, and CYP2E1 among the antifungal drugs investigated [36].
• We found that certain drugs, such as fluconazole, cycloheximide and miconazole, to which Cdr1p confers resistance could also affect in-to-out transbilayer movement of NBD-PE, while the same drugs had no effect on Cdr3p-mediated out-to-in translocation of NBD-PE [37].

Analytical, diagnostic and therapeutic context of miconazole

• RESULTS--Assuming the Medicare-approved charge for a follow-up visit ($21.98), it is less expensive to begin therapy with a prescription drug only if the efficacy rate of miconazole is less than 55%; this threshold efficacy rate varied from 26% (for a $0 total cost of the follow-up visit) to 79% (for an $89 total cost of the follow-up visit) [38].
• Miconazole treatment after renal transplantation [39].
• Patients treated with cytotoxic therapy expected to produce neutropenia lasting two or more weeks were randomly assigned in a double-blind study to receive intravenous miconazole or placebo concomitant with empiric antibiotics to test whether miconazole can prevent fungal sepsis [40].
• Progressive increases in miconazole dosage during the treatment periods were required to produce serum levels above the minimum inhibitory concentrations of the fungal isolates [15].
• In vivo cerebral blood flow measurements were made in adult rats by laser-Doppler flowmetry after administration of glutamate into the subdural space of the rat before and after treatment with miconazole [26].

References