Diflucan
Pharmacokinetics of fluconazole in saliva and plasma after administration of an oral suspension and capsules.

Koks CH, Meenhorst PL, Hillebrand MJ, Bult A, Beijnen JH.

Department of Pharmacy, Slotervaart Hospital, Amsterdam, The Netherlands.

The concentrations of fluconazole were determined at steady state in the saliva and plasma of 10 healthy volunteers after ingestion of fluconazole as capsules and after flushing the mouth for 2 min with the same dose formulated as an oral suspension and swallowing of the drug. Saliva and plasma samples were analyzed by a validated high-performance liquid chromatographic assay. Flushing and swallowing of the oral suspension resulted in a significantly (P = 0.005) higher mean area under the concentration-versus-time curve (AUC) from 0 to 24 h in saliva (89.13 +/- 23.42 mg.h/liter) than that obtained after ingestion of the same dose as capsules (69.27 +/- 12.89 mg . h/liter). The calculated mean maximum concentration in saliva just after swallowing of the suspension was 97.99 +/- 6.12 mg/liter. The peak fluconazole concentration in saliva after the ingestion of the capsules was 3.55 +/- 0.40 mg/liter. The fluconazole oral suspension and capsules resulted in comparable concentrations and AUCs in plasma. Thus, because of a higher local level of drug exposure in terms of both higher peak concentrations in saliva and a higher salivary AUC, the fluconazole oral suspension has theoretical advantages over the capsule formulation in the treatment of oropharyngeal candidiases.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8843308&dopt=Abstract fluconazole Diflucan



Diflucan
In vitro studies of two triazole antifungal agents (voriconazole [UK-109,496] and fluconazole) against Candida species.

Barry AL, Brown SD.

Clinical Microbiology Institute, Tualatin, Oregon 97062, USA.

A new triazole derivative (voriconazole or UK-109,496) and fluconazole were tested against 249 isolates of Candida spp. representing six species. Voriconazole was 10 to 100 times more potent than fluconazole. Strains with decreased susceptibility to fluconazole were inhibited by relatively low concentrations of voriconazole.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8843312&dopt=Abstract fluconazole Diflucan



Diflucan
Response to fluconazole by 23 patients with human immunodeficiency virus infection and oral candidiasis: pharmacological and mycological factors.

Lacassin F, Damond F, Chochillon C, Longuet P, Lebras J, Vilde JL, Leport C.

Department of Infectious Tropical Diseases, Bichat-Claude Bernard Hospital, Paris, France.

The MICs of fluconazole for strains of Candida species and the levels of fluconazole in serum were determined at day 0 and day 14 for 23 human immunodeficiency virus-infected patients with oral candidiasis who were treated orally with 100 mg of fluconazole per day for 14 days. Among the 23 patients, 11 (48%) were not clinically cured and had persistent isolation of Candidiasis albicans (n = 10) and/or presence of non-C. albicans (n = 6). Clinical response could be predicted by the susceptibility of the strain to fluconazole determined at day 0. All 12 patients who were cured were infected with a strain for which the MIC was < 0.78 mg/liter. All four patients who were infected with a strain for which the MIC was > 3.12 mg/liter experienced clinical failure. These data suggest that a C. albicans strain could be defined as being susceptible when the MIC of fluconazole is < 0.78 mg/liter and as being resistant when the MIC is > 3.12 mg/liter.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8843316&dopt=Abstract fluconazole Diflucan



Diflucan
Determination of fluconazole in human plasma by micellar electrokinetic capillary chromatography with detection at 190 nm.

von Heeren F, Tanner R, Theurillat R, Thormann W.

Department of Clinical Pharmacology, University of Bern, Switzerland.

The determination of fluconazole (Diflucan) in human plasma by micellar electrokinetic capillary chromatography (MECC) with on-column UV absorption detection at 190 nm from primary, deproteinized and extracted plasma samples is discussed. Direct injection of plain plasma or of the supernatant after protein precipitation with acetonitrile is shown to permit the determination of fluconazole drug levels of > 5 micrograms/ml only. With liquid-liquid extraction employing dichloromethane, the detection limit is about 1 microgram/ml. After extraction using disposable solid-phase C18 cartridges and 1 ml of plasma, however, drug levels as low as 100 ng/ml can be determined unambiguously. Calibration graphs between 0.125-25.0 micrograms/ml (seven data points) are shown to be linear, with a regression coefficient r > 0.999. for fluconazole plasma levels of 5 micrograms/ml, intra-day and inter-day imprecisions (n = 10) are about 2 and 5%, respectively. Using the same solid-phase extraction procedure, 44 fluconazole plasma levels that were determined by MECC are shown to agree well with those obtained by HPLC and elucidated pharmacokinetic data compare well with those found in the literature. The advantages of using MECC instead of HPLC for the determination of fluconazole plasma levels and pharmacokinetics are the high resolution efficiency, low-cost capillary columns and the small consumption of inexpensive and environmentally friendly chemicals.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8843685&dopt=Abstract fluconazole Diflucan



Diflucan
Susceptibilities of Candida spp. to antifungal agents visualized by two-dimensional scatterplots of relative growth.

Odds FC, Dams G, Just G, Lewi P.

Department of Bacteriology and Mycology, Janssen Research Foundation, Beerse, Belgium.

The growth of 811 clinical yeast isolates in the presence of single concentrations of antifungal agents was measured spectrophotometrically and expressed as a percentage of growth in inhibitor-free control cultures. Two-dimensional scatterplots of the relative growth data allowed for the simple visual determination of some susceptibility trends, including correlations in relative growth between different agents and in relative susceptibilities between different yeast species. A positive susceptibility correlation was found for relative growth results with the azole antifungal agents fluconazole, itraconazole, and ketoconazole for 504 Candida albicans isolates. The relative growth scatterplots for fluconazole versus itraconazole showed that 50 (9.9%) of 504 C. albicans isolates were outliers with respect to the 95% confidence limits for a line of correlated relative growth established with an initial test panel of 59 isolates of this species. The outlying isolates were relatively less susceptible to fluconazole than to itraconazole under the conditions of the test. Most of the outliers were received in 1993 and 1994; only 3.9% of the isolates received in 1991 and 1992 and 1.7% of the isolates received before 1991 showed this differential susceptibility. In addition, most of the outliers came from patients with human immunodeficiency virus infections. The relative growth scatterplots confirmed the known high susceptibility of most Candida parapsilosis isolates to both fluconazole and itraconazole and the specifically low susceptibility of Candida krusei isolates to fluconazole. The scatterplots also illustrated a tendency towards lower (and correlative) relative growth among oral isolates obtained from AIDS patients who responded to azole antifungal treatment than among isolates from clinical nonresponders.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8851576&dopt=Abstract fluconazole Diflucan



Diflucan
Fluconazole disk diffusion procedure for determining susceptibility of Candida species.

Barry AL, Brown SD.

Clinical Microbiology Institute, Tualatin, Oregon 97062, USA.

A simple disk diffusion test was defined for quick determination of the susceptibility of Candida species to fluconazole. The standard macrotube dilution reference method, the fluconazole E test, and a 25-microgram fluconazole disk test were all performed with each of 250 Candida species selected to provide a broad range of fluconazole MICs. All three methods were in excellent agreement. On RPMI 1640-glucose agar, isolates with inhibition zone diameters of > or = 19 mm were all susceptible (MIC, < or = 8.0 micrograms/ml) by the E test and 94% were susceptible by the macrotube method. Strains with smaller zones were either resistant, intermediate (dose-dependent susceptibility), or susceptible by the reference methods. The disk test did not adequately separate fully resistant strains from those with dose-dependent susceptibility: additional quantitative tests are needed for the few strains that are not unequivocally susceptible by the disk method.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8862576&dopt=Abstract fluconazole Diflucan



Diflucan
Antifungal prophylaxis for secondary fungal peritonitis in peritoneal dialysis patients.

Wadhwa NK, Suh H, Cabralda T.

Department of Medicine, State University of New York at Stony Brook, USA.

Our objective was to evaluate antifungal prophylaxis for secondary fungal peritonitis in peritoneal dialysis patients. The study was designed to investigate antifungal prophylaxis for fungal peritonitis and to compare the incidence of fungal peritonitis without (January, 1991-July, 1993) and with (August, 1993-December, 1995) antifungal prophylaxis. In a tertiary-referral university hospital, 122 end-stage renal disease (ESRD) patients (77 male, 45 female) during period A (1/91-7/93) were observed for 1832 patient-months with no antifungal prophylaxis. One hundred and twelve ESRD patients (71 male, 41 female) during period B (8/93-12/95) were observed over 1705 patient-months with antifungal prophylaxis with fluconazole. Fluconazole 200 mg was given orally (po) as first dose at the onset of antibiotic therapy, then 100 mg po every other day, and was continued for one week after the antibiotic therapy. Forty-nine patients (28 male, 21 female; mean age 48.8 years) developed 105 episodes of peritonitis during period A. Forty-eight patients (36 male, 12 female; mean age 53.8 years) developed 95 episodes of peritonitis during period B. Fifteen episodes of fungal peritonitis occurred over 1832 patient-months during period A. while four episodes of fungal peritonitis were observed over 1705 patient-months during period B. Twelve episodes of secondary fungal peritonitis occurred during period A, while only two episodes occurred during period B. This incidence of secondary fungal peritonitis was significantly reduced with antifungal prophylaxis (p < 0.02). No side effect of fluconazole was observed. In conclusion, secondary fungal peritonitis was significantly decreased following fluconazole antifungal prophylaxis at our center.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8865899&dopt=Abstract fluconazole Diflucan



Diflucan
Therapy of systemic histoplasmosis in immunosuppressed mice with the triazole D0870.

Clemons KV, Martinez M, Homola ME, Stevens DA.

Department of Medicine, Santa Clara Valley Medical Center, San Jose, CA 95128, USA.

Because histoplasmosis is a life-threatening disease in AIDS and other compromised patients, we examined the efficacy of D0870 (Zeneca) in immunosuppressed mice against systemic histoplasmosis. Oral therapy with fluconazole given once daily (QD) was ineffective in prolonging survival, whereas itraconazole given once or twice daily (BID), fluconazole given BID or D0870 given QD or given every other day (QOD) were efficacious (P < 0.001). Burdens of Histoplasma capsulatum in the liver and spleen of survivors showed that D0870 given QD or QOD and itraconazole given BID caused dose-responsive reduction of infectious burden. Infection was cleared more readily from the liver than from the spleen. Overall, D0870 was > or = 20-fold more efficacious than fluconazole or itraconazole and itraconazole was > ten-fold better than fluconazole for the treatment of systemic histoplasmosis in the immunosuppressed model.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8873882&dopt=Abstract fluconazole Diflucan