Fluconazole levels in plasma and vaginal secretions of patients after a 150-milligram single oral dose and rate of eradication of infection in vaginal candidiasis

Abstract

Mean peak concentrations of fluconazole in plasma and vaginal secretions of females after a 150-mg single oral dose were shown to be 2.82 ,g/ml and 2.43 ,g/g, respectively. Our results indicate that clinically efficacious concentrations of fluconazole in vaginal secretions are easily achieved after this single oral dose.Fluconazole is a new bis-triazole antifungal agent which has shown excellent activity against candidiasis both in animal models and in patients with oropharyngeal or vaginal candidiasis (1, 3, 4). As well as having good absorption after oral administration (>90% bioavailability), a long plasma half-life (25 h), and low protein binding (12%), fluoconazole is rapidly distributed in body tissue fluids (2). The activity of fluoconazole against oropharyngeal candidiasis has been partially attributed to its presence in saliva, where levels of magnitude similar to those in plasma are attainable. Fluconazole would be expected to achieve levels similar to those in plasma in both vaginal secretions and tissues to account for its success in the treatment of vaginal candidiasis. The aim of the present study was to determine the simultaneous levels of fluconazole in plasma and vaginal secretions in patients receiving treatment for vaginal candidiasis and to measure the rate of eradication of fungal infection. We also report the first use of a capillary gas chromatographic assay combined with ion trap detection for measurement of fluconazole in samples of small volume.From a group of patients participating in a multicenter study to determine the efficacy, safety, and toleration of fluconazole in the treatment of vaginal candidiasis (results of which will be published separately), patients who worked locally were approached for additional informed consent to enter this investigation. Only patients aged 18 years or older, with a clinical diagnosis of vaginal candidiasis (including symptoms of either vaginal pruritus or burning), who were willing to refrain from sexual intercourse until 7 days after fluconazole treatment were allowed to enter. Excluded were those who were either pregnant or lactating; had any other clinically relevant disease or impairment of renal or hepatic function; had concomitant venereal disease, trichomoniasis, or nonspecific vaginitis; were undergoing any other antifungal treatment; were taking any drugs that are cleared predominantly by metabolism and that have a low therapeutic ratio; or had taken any investigational drug in the previous month. Thus the first nine females (mean age, 30 years; range, 23 to 41 years) who agreed to return were enrolled in the study.Just before a patient received an oral 150-mg dose (three 50-mg capsules) of fluconazole, samples of blood and of vaginal secretion were taken. Further samples were taken at * Corresponding author. 2, 8, 24, 72, 120, and 168 h postdosing. Blood samples were collected in heparin tubes, and plasma was separated immediately by centrifugation and stored at -20°C until assayed. Vaginal secretion samples were collected by suction into...

Efficacy of the Clinical Agent VT-1161 against Fluconazole-Sensitive and -Resistant Candida albicans in a Murine Model of Vaginal Candidiasis

“…Both drugs fully equilibrated into the vaginal tissue from the blood. The VT-1161 vaginal tissue data were consistent with those for the single-dose PK study, and the fluconazole data were consistent with those in a previous publication (21). Finally, it is noted that the strain of mouse used in the PK study (BALB/c) was different from the strain used in the model (CBA/J), and some PK components may differ.…”

Tissue Penetration of Antifungal Agents

“…Fluconazole is used extensively for treating urogenital infections caused by Candida spp. Consequently, there is a relative abundance of clinical data related to the concentrations of fluconazole within gynecological tissues and secretions (67,200,201), testicular (71) and prostatic (71,202) tissues, and prostatic fluids (203) (Fig. 7).…”

Pure versus Complicated Vulvar Vestibulitis: A Randomized Trial of Fluconazole Treatment

“…Fluconazole is water-soluble and highly penetrative to various tissues [8]. It inhibits the fungal enzyme 14·-dimethylsterolase, thus selectively blocking the fungal cytochrome P 450 from building the cell wall ergosterol, and hence is fungicidal [8,9]. It has an excellent activity against Candida albicans and other candidal strains, and has gained popularity over the other oral antifungal agents, as it is devoid of hepatic side effects [9].…”

“…Consequently, the use of fluconazole, an oral preparation of a highly potent antifungal triazole, has been recommended [7]. Fluconazole is water-soluble and highly penetrative to various tissues [8]. It inhibits the fungal enzyme 14·-dimethylsterolase, thus selectively blocking the fungal cytochrome P 450 from building the cell wall ergosterol, and hence is fungicidal [8,9].…”