Miconazole absorption

Ketoconazole. For treatment of systemic mycoses with amphotericin B or miconazole, the patient must be admitted to a hospital. This is not always possible, particularly in areas where systemic mycoses occur frequently, nor is it always desirable, because of the expense. For these reasons, it was desirable to find an antimycotic that combined safety and broad-spectmm activity with oral adraiinistration. Ketoconazole (10), which is orally active, met most of these requirements. This inhibitor of the ergosterol biosynthesis is an A/-substituted imidazole, that differs from its precursors by the presence of a dioxolane ring (6,7). Ketoconazole is rapidly absorbed in the digestive system after oral adrninistration. Sufficient gastric acid is required to dissolve the compound and for absorption. Therefore, medication that affects gastric acidity (for example, cimetidine and antacids) should not be combined with ketoconazole. 

Figure 6.11 shows the measured absorption spectra of miconazole (reference and sample). As precipitation takes place to varying degrees at different pH values, the spectra of the sample solutions change in optical densities, according to Beer s law. This can be clearly seen in Fig. 6.12 for the sample spectra, where the sample spectra have the lowest OD values at pH 9.0 and systematically show higher OD values... 

The ultraviolet absorption spectrum of miconazole nitrate in methanol (0.0104%) shown in Fig. 3 was recorded using a Shimadzu Ultraviolet-visible spectrophotometer 1601 PC. The compound exhibited three maxima at 264, 272, and 280 nm. Clarke reported the following Methanol 264 and 272 nm = 17a), 282 nm [2]. 

The infrared absorption spectrum of miconazole nitrate was obtained in a KBr pellet using a Perkin-Elmer infrared spectrophotometer. The IR spectrum is shown in Fig. 4, where the principal peaks were observed at 3140, 3070, 2995, 2920, 1566, 1525, 1445, 1385, 1310, 1070, and 710 cm-1. Assignments for the major infrared absorption band are provided in Table 2. Clarke reported principal peaks at 1085, 1319, 827, 1302, 1038, and 812 cm-1 (miconazole nitrate, KBr disc) [2]. 

Fig. 4. Infrared absorption spectrum of miconazole nitrate (KBr pellet).

Table 2. Vibrational assignments for miconazole nitrate infrared absorption bands...

Test 2. According to the general method (2.2.24), examine miconazole by infrared absorption spectrophotometry, comparing with the spectrum obtained with miconazole CRS. Examine the substance as discs prepared using potassium bromide R. 

Test 1. Shake a quantity of the gel containing 20 mg of miconazole with sufficient methanol to produce a 0.05% (w/v) solution. The light absorption of this solution, Appendix II B, in the range 250-350 nm exhibits two maxima at 272 and 280 nm and a broad shoulder at about 263 nm. 

Test 1. Mix a quantity containing 40 mg of miconazole nitrate with 20 mL of a mixture of 1 volume of 1 M sulfuric acid and 4 volumes of methanol and shake with two 50 mL quantities of hexane, discarding the organic layers. Make the aqueous phase alkaline with 2 M ammonia and extract with two 40 mL quantities of chloroform. Combine the chloroform extracts, shake with 5 g of anhydrous sodium sulfate, filter, and dilute the filtrate to 100 mL with chloroform. Evaporate 50 mL to dryness and dissolve the residue in 50 mL of a mixture of 1 volume of 0.1 M hydrochloric acid and 9 volumes of methanol. The light absorption of the resulting solution, Appendix II B, in the range 230-350 nm exhibits maxima at 264, 272, and 282 nm. 

Test 1. Carry out the infrared test according to the general procedure <197 K>. The infrared absorption spectrum of a potassium bromide dispersion of it, previously dried, exhibits maxima only at the same wavelength as that of a similar preparation of USP miconazole RS. 

Test 2. Transfer 40 mg to a 100 mL volumetric flask, dissolve in 50 mL of isopropyl alcohol, add 10 mL of 0.1 N hydrochloric acid, dilute with isopropyl alcohol to volume, and mix the ultraviolet absorption spectrum of this solution exhibits maxima and minima at the same wavelength as that of a similar solution of USP Miconazole RS, concomitantly measured. 

Test 2. When the test is carried out according to the general procedure < 197 U>, the ultraviolet absorption spectrum of a 1 in 2500 solution of miconazole nitrate in a 1 in 10 solution of 0.1 N hydrochloric acid in isopropyl alcohol exhibits maxima and minima at the same wavelengths as that of a similar preparation of USP Miconazole Nitrate RS, concomitantly measured. 

Cavrini et al. [32] reported the development of a colorimetric method for the determination of miconazole nitrate in pharmaceutical preparation. The method is based on the formation of a yellow complex between the drug and bromocresol green. The absorption peak of this complex, extracted by chloroform over the pH 2—4 range, was at 424 nm, and linear response was obtained from 3—13 pg/mL. The molar absorptivity of the complex in chloroform was 1.845 x 104. This procedure is suitable for the analysis of miconazole nitrate in commercial dosage forms. 

Hasegawa et al. [76] measured miconazole serum concentration by a high performance liquid chromatographic method. The authors assessed whether the internal standard method produced an intra-assay error and found that the method gave more precise and more reproducible results compared to the absorption calibration curve method. With 0.5 pg/mL of miconazole, the coefficient of variation produced by that method was 3.41%, whereas that of the absorption calibration curve method was 5.20%. The concentration of absorptions calibration curve method showed higher values than the internal standard method. This indicated that the internal standard method was far more precise in measuring the miconazole serum concentrations than the absorption calibration curve method. 

Ohzawa et al [112] studied the absorption, distribution, and excretion of 14C miconazole in rats after a single administration. After the intravenous administration of 14C miconazole at a dose of 10 mg/kg to the male rats, the plasma concentration of radioactivity declined biophysically with half-lives of 0.76 h (a phase) and 10.32 h (/ phase). After oral administration of 14C miconazole at a dose of 1, 3, or 10 mg/kg to male rats, the plasma concentration of radioactivity reached the maximum level within 1.25 h, after dosing and the decline of radioactivity after the maximum level was similar to that after intravenous administration. At a dose of 30 mg/kg, the pharmacokinetic profile of radioactivity in the plasma was different from that at the lower doses. In the female rats, the plasma concentration of radioactivity declined more slowly than that in male rats. The tests were conducted on pregnant rats, lactating rats, bile-duct cumulated male rats. Enterohepatic circulation was observed. In the in situ experiment, 14C miconazole injected was observed from the duodenum, jejunum, and/or ileum, but not from the stomach. 

Ohzawa et al. [113] studied the absorption, excretion, and metabolism of miconazole after a single oral administration of 14C miconazole at a dose of 10 mg/kg to male dogs. After administration of 14C miconazole, the blood concentration of radioactivity reached the maximum level at 4 h, and then declined slowly with a half-life of about 26 h. The plasma concentration reached the maximum level at 5 h and then declined slowly with a half-life of 30 h. After the administration of miconazole, the plasma concentration of the unchanged form reached the maximum level at 3 h and then rapidly declined with half-life of about 4.3 h. Within 168 h after administration of 14C miconazole, urinary and fecal excretion amounted to about 6% and 66% of the administration radioactivity, respectively. After administration of 14C miconazole, the plasma concentration of the unchanged form rapidly declined, but the plasma level of two major metabolites reached maximum at 5 and 12 h, respectively and then declined. 

Ohzawa et al [114] studied the absorption, distribution, and excretion of 14C miconazole in male rats during and after consecutive oral administration at a dose of 10 mg/kg once a day for 15 days. During consecutive administration, the plasma concentration of radioactivity reached the steady state on day 4 and was 0.48 approximately 0.52 pg eq./mL at 24 h after each dose. After the final dose, the plasma concentration of radioactivity reached the maximum level of 1.67 pg eq./ mL at 7.5 h and declined with a half-life of about 18.68 h. The area under the curve 24 h was 28.3 pg h/mL, which is close to the area under the curve O-oo of a single oral dose. 

GI absorption of many poorly soluble drugs depends on small intestinal transit, as demonstrated for ketoprofen, nifedipine, haloperidol, miconazole, and others. Small intestinal transit rate and transit time become important factors in drug absorption, particularly when the ratio of dose to solubility is high and dissolution rate is very slow or when the drug is... 

T Pancreatic insulin release Metformin Peripheral insulin sensitivity hepatic glucose output/production i intestinal glucose absorption Dose Ist-line (naive pts), 1.25/250 mg PO daily-bid 2nd-line, 2.5/500 mg or 5/500 mg bid (max 20/2000 mg) take w/ meals, slowly T dose hold before 48 h after ionic contrast media Caution [C, -] Contra SCr >1.4 mg/dL in females or >1.5 mg/dL in males hypoxemic conditions (sepsis, recent MI) alcoholism metabolic acidosis liver Dz Disp Tabs SE HA, hypoglycemia, lactic acidosis, anorexia, N/V, rash Additional Interactions T Effects W/ amiloride, ciprofloxacin cimetidine, digoxin, miconazole, morphine, nifedipine, procainamide, quinidine, quinine, ranitidine, triamterene,... 

Miconazole (Monistat) is a broad-spectrum imidazole antifungal agent used in the topical treatment of cutaneous dermatophyte infections and mucous membrane Candida infections, such as vaginitis. Minimal absorption occurs from skin or mucous membrane surfaces. Local irritation to skin and mucous membranes can occur with topical use headaches, urticaria, and abdominal cramping have been reported with treatment for vagiiutis. 

It is orally effective broad spectrum imidazole antifungal drug. It is useful in both dermatophytosis and deep mycosis. Oral absorption is facilitated by gastric acidity. It is highly protein bound, metabolised in liver and metabolites are excreted in urine and faeces. Its spectrum is similar to that of miconazole and is more active against Coccidioides. 

The two azoles most commonly used topically are clotrimazole and miconazole several others are available (see Preparations Available). Both are available over-the-counter and are often used for vulvovaginal candidiasis. Oral clotrimazole troches are available for treatment of oral thrush and are a pleasant-tasting alternative to nystatin. In cream form, both agents are useful for dermatophytic infections, including tinea corporis, tinea pedis, and tinea cruris. Absorption is negligible, and adverse effects are rare. 

Daneshmend, T.K. 1986. Systemic absorption of miconazole from the vagina. J Antimicrob Chemother 18 507. 

Vukovich, R.A., A. Heald, and A. Darragh. 1977. Vaginal absorption of two imidazole antifungal agents, econazole and miconazole. Clin Pharmacol Therap 21 121. 

ITRACONAZOLE, KETOCONAZOLE, MICONAZOLE, POSACONAZOLE H2 RECEPTOR BLOCKERS 1 plasma concentrations and risk of treatment failure 1 absorption of these antifungals as t gastric pH Avoid concomitant use. If unable to avoid combination, take H2 blockers at least 2-3 hours after the antifungal. Use an alternative antifungal or separate doses by at least 2 hours and give with an acidic drink, e.g. a carbonated drink t dose of antifungal may be required... 

Miconazole has been evaluated as a topical, oral, and intravenous agent. Its absorption is slightly better than that of clotrimazole, but is still insufficient for use as a systemic agent, particularly in view of its relatively short half-life of around 8-9 hours (1). Miconazole has also been given intravenously and intrathecally. It is highly protein-bound and does not diffuse well into the CSF however, it does penetrate readily into synovial and vitreous fluids (2). 

B. Azole antifungals include systemic agents such as keto-conazole, fluconazole, itraconazole, and voriconazole. Topical agents used for the treatment of vaginal candidiasis and thrush include miconazole and clotrimazole. The pharmacologic properties of the systemic azoles differ considerably. Ketoconazole, the first oral azole developed, has poor bioavailability and requires an acidic environment for enhanced absorption. Thus, initial studies required ketoconazole to be administered with a cola to increase bioavailability. Fluconazole, unlike itraconazole and ketoconazole, is hydrophillic and has increased penetration across the blood-brain barrier. Fluconazole is also the only azole that is renally eliminated. 

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