Pharmacokinetics of ciprofloxacin and fluocinolone acetonide otic solution in pediatric patients

• Published in: American journal of otolaryngology Vol. 43; no. 5; p. 103573
• Main Authors: Spektor, Zorik, Hussain, Iftikhar, Van Leeuwen, Richard Neil, Goudy, Steven, Esterhuizen, Kenneth, Meyer, Ryan, Hedrick, James
• Format: Journal Article
• Language: English
• Published: Maryland Heights Elsevier Inc 01.09.2022; Elsevier Limited
• Subjects: Acute otitis media with tympanostomy tubes; Antibiotics; Blood; Caregivers; Ciprofloxacin; Ciprofloxacin plus fluocinolone acetonide; Clinical trials; Drug dosages; Ear; Ear canal; FDA approval; Informed consent; Liquid chromatography; Mass spectrometry; Mass spectroscopy; Otitis media; Patients; Pediatrics; Pharmacokinetics; Pharmacology; Plasma; Steroids; Streptococcus infections; Tubes; Canada; South Africa; FLUO; Pediatrics; FDA; CIPRO+FLUO; CIPRO; AOE; Acute otitis media with tympanostomy tubes; AOMT; PK; Pharmacokinetics; Ciprofloxacin plus fluocinolone acetonide; LC-MS-MS
• ISSN: 0196-0709; 1532-818X; 1532-818X
• DOI: 10.1016/j.amjoto.2022.103573

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). 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. No detectable concentrations of ciprofloxacin or fluocinolone acetonide in plasma were observed (<1 ng/mL). These results demonstrated negligible systemic exposure to ciprofloxacin and fluocinolone acetonide following topical otic administration in pediatric patients with AOMT.