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Objective: A study was conducted to establish the bioequivalence between a newly developed cyclosporin A (CsA) oral formulation, Deximune® soft-gelatin capsules (Dexcel Ltd.) and Sandimmune Neoral® (Novartis Inc.). Materials and methods: The clinical investigation was designed as a randomized, open-labeled, two-period, two-treatment crossover study, in 24 healthy fasted male volunteers. The subjects were administered a single 200 mg CsA dose of either formulation. Serial venous blood samples were obtained over 24 hours after each administration to measure CsA in whole blood by a specific TDx-immunoassay. In addition, the comparative drug release rate was assessed using a dissolution apparatus test according to the USP-24 method. Results: For both treatments, a mean maximum blood concentration (C max ) of approximately 1,200 ng/ml was obtained at about 1.6 hours (t max ) after administration and the geometric mean of the area under the blood concentration-time curve (AUC) both for test and reference was approximately 4,900 ng x h/ml. Bioequivalence was conclusively demonstrated for both rate (C max andt max ) and extent (AUC) of CsA absorption, between the two treatments. Moreover, the CsA blood concentration measurement at 2 hours after administration (C 2 ), demonstrated equivalent results between the two products. The point estimates and their 90% confidence intervals were within the respective equivalence ranges for the pharmacokinetic parameters and were included in the range for drugs with a narrow therapeutic index. The comparative dissolution test for both formulations showed an in vitro release rate of more than 90% within 15 minutes. Conclusions: Based on the results, the two oral CsA formulations compared are bioequivalent and can be interchanged without need for dosage adjustment.

Bloodstream infections with Candida are often lethal and have been reported to be increasing in frequency. The current retrospective study describes the magnitude and epidemiological characteristics of candidemia in all western-type hospital facilities in Israel in 1994. Comprehensiveness of the data from the reporting hospitals was checked by cross-study of the data from the infectious diseases records and from the hospitalization records. Vital status of all reported cases was evaluated 1 year after the diagnosis. Data on 298 newly diagnosed cases of candidemia were received from 14 of the 18 general hospitals in Israel. The proportion of candidemia in the Israeli hospitals ranged from 0.1 to 0.01% of all admissions, with a mean of 0.05%. The incidence of candidemia differed significantly between the wards from 4-5/10,000 in general surgery and internal medicine wards to about 60/10,000 and 80/10,000 in intensive care and preterm units, respectively. Of all detected cases 53.6% were Candida albicans. Another nine specific species of Candida (mainly Candida parapsilosis, Candida tropicalis and Candida glabrata) were detected, with major differences between the various hospitals. The species of Candida differed significantly by sex and age. Of the cases of candidemia 21.5% died within 30 days of the isolation of the pathogen. The one-year mortality rate was 31.9%. Species-specific 30-day mortality rate was highest for C. glabrata. Throughout the analysis, C. glabrata emerged as a unique cause of candidemia, producing higher mortality, appearing at a younger age and predominating among females.

To evaluate the penetration of ciprofloxacin, a new wide-spectrum oral antibiotic, into the vitreous, ciprofloxacin was administered orally to 21 patients who were scheduled to undergo vitreal surgery. Seven patients received 750 mg ciprofloxacin 4 hr before surgery (group I), seven patients received this dose 8 hr before surgery (group II), and seven patients received two 750-mg doses of oral ciprofloxacin every 12 hr. The last dose was administered 12 hr before surgery (group III). Vitreous and blood samples were collected simultaneously and assayed for ciprofloxacin concentrations by bioassay and high-performance liquid chromatography.

Twenty-three consecutive patients with malignant external otitis (MEO) were treated with oral ciprofloxacin, 1.5-2.25 g/day for 6 weeks. Treatment was combined with local surgical debridement. Patients were discharged early for ambulatory follow-up. Few minor side effects were reported, and full compliance with the study drug was observed. In 21 patients cure was achieved; in 2 the response was not adequate. Oral ciprofloxacin is an effective, convenient, nontoxic, economically justified alternative to the combination intravenous therapy previously advocated.