Miconazole in coccidiodomycosis. II. Therapeutic and pharmacologic studies in man.
Fourteen patients with chronic coccidioidomycosis, many of whom had complicating concurrent diseases and/or had failed to respond to amphotericin therapy, were treated with intravenous miconazole, a synthetic imidazole drug previously shown to be effective in experimental murine coccidioidomycosis. Up to 3.6 g/day was given for up to three months. 7inimal inhibitory concentrations of mycelial and endospore phases of all clinical isolates of C. immitis were less than 2.0 mug/ml. Peak concentrations in the blood of up to 7.5 mug/ml (by assay against C. immitis in vitro) were achieved. Doses above 9 mg/kg or 350 mg/m2 were more efficacious in producing blood levels over 1 mug/ml. Serum protein binding, determined by several methods, was approximately 90 per cent. The disappearance of bioactive drug from blood after infusion has a rapid initial phase (t1/2 approximately 30 minutes) and a final plateau (t1/2 approximately 20 hours). Eight patients had objective evidence of response, three had slight or equivocal responses, two could not be evaluated, and one was a treatment failure. Side effects were generally uncommon, minor and transient except for phlebitis. Infusion into central venous catheters appears to circumvent this problem. Miconazole is a potentially useful drug in the treatment of coccidioidomycosis.
D000328:Adult; D000818:Animals; D003045:Coccidioides / Q000187:drug effects; D003047:Coccidioidomycosis / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use*; D007700:Kinetics; D008297:Male; D008825:Miconazole / Q000008:administration & dosage / Q000009:adverse effects / Q000134:cerebrospinal fluid / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D008875:Middle Aged; D011485:Protein Binding; D013183:Sputum / Q000378:metabolism
D007093:Imidazoles; D008825:Miconazole