Printed from: Clarke's Analysis of Drugs and Poisons, London: Pharmaceutical Press. Electronic version, 2005.

Proprietary name. Daktarin 1-[2-(2,4-Dichlorophenyl)-2-[(2,4-dichlorophenyl)methoxy]ethyl]-1-H-imidazole C18H14Cl4N2O = 416.1CAS22916478

A white crystalline powder.

Very slightly soluble in water; very soluble in chloroform; soluble in most other organic solvents.

Miconazole NitrateProprietary names. Albistat; Daktarin (cream); Dermonistat; Gyno-Daktarin; Micatin; Monistat.C18H14Cl4N2O,HNO3 = 479.1CAS22832877

A white crystalline powder. M.p. about 182.

Very slightly soluble in water and ether; soluble 1 in 140 of ethanol; slightly soluble in chloroform.

Dissociation Constant. pKa6.7.

Thinlayer Chromatography. System TARf 73; system TBRf 11; system TCRf 67; system TERf 80; system TFRf 07; system TLRf 37; system TADRf 56; system TAERf 77; system TAFRf 80. (Dragendorff spray.)

Gas Chromatography. System GARI 2965.

Ultraviolet Spectrum. Methanol264, 272 (A11=17a), 280 nm.

Miconazole Antifungal

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Infrared Spectrum. Principal peaks at wavenumbers 1085, 1319, 827, 1302, 1038, 812 cm1 (miconazole nitrate, KBr disk).

Mass Spectrum. Principal peaks at m/z 159, 161, 81, 335, 333, 163, 337, 205.

Quantification

GAS CHROMATOGRAPHY. In plasma: S. C. Szathmary and I. Luhmann,J. Chromatogr.,1988, 425, 193196. In serum: limit of detection 1 g/L, ECDP. T. Mnnistet al.,Antimicrob. Agents Chemother.,1982, 21, 730733.HIGH PERFORMANCE LIQUID CHROMATOGRAPHY. In plasma: limit of detection 5 g/L, UV detection (=230 nm) M. Kobylinska et al.,J. Chromatogr. B Biomed. Appl.,685, 191195. In vaginal fluid: K. Selinger et al.,J. Chromatogr.,1988, 434, 259264. In saliva: limit of detection 500 g/L, UV detectionA. Turner and D. W. Warnock,J. Chromatogr., 1982, 227; B Biomed. Appl.,16, 229232.

BIOASSAY. In serumA. Espinel-Ingroff et al.,Antimicrob. Agents Chemother.,1977, 11, 365368.

NOTE. For a rapid HPLC screen of antifungal agents in serum see T. K. Ng et al.,J. Antimicrob. Chemother.,1996, 37, 465472.

Disposition in the Body. Incompletely absorbed after oral administration and poorly absorbed after topical administration. Metabolised by oxidation to 2,4dichloromandelic acid and 2-(2,4dichlorobenzyloxy)-2-(2,4dichlorophenyl)acetic acid which are both inactive. About 10 to 20% of an oral or IV dose is excreted in the urine in 6 days, with only about 1% of the dose as unchanged drug. About 50% of an oral dose is eliminated in the faeces, mostly unchanged.

THERAPEUTIC CONCENTRATIONFollowing an IV infusion of 522 mg to 4 subjects, plasma concentrations of 2.0 to 9.1 g/mL (mean 6.2) were reported at the end of the infusion [P. J. Lewi et al.,Eur. J. Clin. Pharmacol.,1976, 10, 4954].

TOXICITY. For a report of convulsions after miconazole overdose see K. Coulthard et al.,Med. J. Aust.,1987, 146, 5758.

HALFLIFE. Plasma halflife, about 24 h.

VOLUME OF DISTRIBUTION. About 20 L/kg.

PROTEIN BINDING. In plasma, about 92%.

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NOTE. For a review of the pharmacokinetics of systemic antifungal drugs see T. K. Daneshmend and D. W. Warnock,Clin. Pharmacokinet.,1983, 8, 1742.

Dose. 0.6 to 3.6 g daily by IV infusion; 1 g daily by mouth. Pharmaceutical Press 2005

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