Pharmacokinetics of ciprofloxacin and fluocinolone acetonide otic solution in pediatric patients.

PURPOSE: To describe the pharmacokinetics (PK) of ciprofloxacin 0.3 % and fluocinolone acetonide 0.025 % otic solution (CIPRO+FLUO), ciprofloxacin 0.3 % otic solution alone (CIPRO), and fluocinolone acetonide 0.025 % otic solution alone (FLUO) administered into the middle ears of pediatric patients with Acute Otitis Media with Tympanostomy Tubes (AOMT). MATERIALS AND METHODS: We performed a PK analysis of patients who participated in two multicenter, randomized, double-blind AOMT clinical trials (SALVAT studies CIFLOTIII/10IA02 and CIFLOTIII/10IA04). Each patient received 0.25 mL of CIPRO+FLUO, CIPRO, or FLUO twice a day instilled into the ear canal(s) for 7 days to treat AOMT. Blood samples of patients with unilateral AOMT were collected before the administration of the first dose of study medication at Visit 1 (day 1) and within 1-2 h after the last dose on day 7. Blood samples were analyzed to detect ciprofloxacin and fluocinolone acetonide concentrations using two validated liquid chromatography-tandem mass spectrometry (LC-MS-MS) methods, with the lower limit of quantification for ciprofloxacin and fluocinolone acetonide in plasma samples being 1 ng/mL. Thirty randomly selected patients between 10 months and 10 years of age (mean age, 4.4 years) were included in the study. Although all available samples were analyzed, only PK data of the 22 patients with both samples and unilateral disease were considered for study purposes. RESULTS: No detectable concentrations of ciprofloxacin or fluocinolone acetonide in plasma were observed (<1 ng/mL). CONCLUSIONS: These results demonstrated negligible systemic exposure to ciprofloxacin and fluocinolone acetonide following topical otic administration in pediatric patients with AOMT.

A decrease in bulk water and mannitol and accumulation of trehalose and trehalose-based oligosaccharides define a two-stage maturation process towards extreme stress resistance in ascospores of Neosartorya fischeri (Aspergillus fischeri).

Fungal propagules survive stresses better than vegetative cells. Neosartorya fischeri, an Aspergillus teleomorph, forms ascospores that survive high temperatures or drying followed by heat. Not much is known about maturation and development of extreme stress resistance in fungal cells. This study provides a novel two-step model for the acquisition of extreme stress resistance and entry into dormancy. Ascospores of 11- and 15-day-old cultures exhibited heat resistance, physiological activity, accumulation of compatible solutes and a steep increase in cytoplasmic viscosity. Electron spin resonance spectroscopy indicated that this stage is associated with the removal of bulk water and an increase of chemical stability. Older ascospores from 15- to 50-day-old cultures showed no changes in compatible solute content and cytoplasmic viscosity, but did exhibit a further increase of heat resistance and redox stability with age. This stage was also characterized by changes in the composition of the mixture of compatible solutes. Mannitol levels decreased and the relative quantities of trehalose and trehalose-based oligosaccharides increased. Dormant ascospores of N. fischeri survive in low-water habitats. After activation of the germination process, the stress resistance decreases, compatible solutes are degraded and the cellular viscosity drops. After 5 h, the hydrated cells enter the vegetative stage and redox stability has decreased notably.