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.

Efficacy and Safety of Ciprofloxacin Plus Fluocinolone in Otitis Media With Tympanostomy Tubes in Pediatric Patients: A Randomized Clinical Trial.

Importance: Acute otitis media with tympanostomy tubes (AOMT) in children commonly presents with otorrhea and negatively affects their daily activities. Objective: To evaluate the efficacy and safety of topical ciprofloxacin, 0.3%, plus fluocinolone acetonide, 0.025%, otic solution relative to ciprofloxacin, 0.3%, otic solution alone and fluocinolone acetonide, 0.025%, otic solution alone in the treatment of AOMT in children. Design, Setting, and Participants: Two twin multicenter, randomized, double-blind clinical trials with identical designs were conducted from June 24, 2011, through June 23, 2014, at ear, nose, and throat pediatric practices, general practices, hospitals, and clinical research centers. The study population comprised 662 children (331 in each trial) with AOMT in at least 1 ear who presented with moderate or severe purulent otorrhea for 3 weeks or less. Data analyses were performed on an intention-to-treat basis. Interventions: Patients were randomly assigned to receive ciprofloxacin plus fluocinolone, ciprofloxacin alone, or fluocinolone alone twice daily for 7 days and were evaluated on days 1 (baseline), 3 to 5 (undergoing therapy), 8 to 10 (end of therapy), and 18 to 22 (test of cure). Main Outcomes and Measures: The primary efficacy measure was time to cessation of otorrhea. The principal secondary end point was sustained microbiological cure, defined as eradication or presumed eradication at end-of-therapy and test-of-cure visits. Results: A total of 662 children participating in the 2 studies were randomized to receive ciprofloxacin plus fluocinolone (n = 223), ciprofloxacin alone (n = 221), or fluocinolone alone (n = 218). The median age was 2.5 years (range, 0.6-12.7 years). The median time to cessation of otorrhea was 4.23 days (95% CI, 3.65-4.95 days) in patients receiving ciprofloxacin plus fluocinolone compared with 6.95 days (95% CI, 5.66-8.20 days) in those receiving ciprofloxacin and not estimable findings in those receiving fluocinolone alone (P < .001). The clinical cure rate at the test-of-cure visit was 80.6% in the ciprofloxacin plus fluocinolone group, 67.4% in the ciprofloxacin group (difference, 13.2%; 95% CI, 5.0%-21.4%; P = .002), and 47.6% in the fluocinolone group (difference, 33.0%; 95% CI, 24.0%-42.0%; P < .001). The sustained microbiological cure rate was 79.7% in the ciprofloxacin plus fluocinolone group vs 67.7% in the ciprofloxacin group (difference, 12.0%; 95% CI, 0.8%-23.0%; P = .04) and 37.6% in the fluocinolone group (difference, 42.1%; 95% CI, 29.3%-54.8%; P < .001). Only 7 (3.1%) of the patients receiving ciprofloxacin plus fluocinolone, 8 (3.6%) of the patients receiving ciprofloxacin, and 10 (4.7%) of the patients receiving fluocinolone presented with adverse events related to study medication. Conclusions and Relevance: The combination of ciprofloxacin plus fluocinolone is more effective than treatment with ciprofloxacin or fluocinolone alone for AOMT, and it is safe and well tolerated in children. Trial Registration: clinicaltrials.gov Identifiers: NCT01395966 and NCT01404611.