Pharmacokinetics otolaryngology

OBJECTIVES: Previously, we developed a novel double-coated sinus stent containing ciprofloxacin (inner layer) and azithromycin (outer layer) (CASS), but released drug concentrations were found to be insufficient for clinical usage. Our objectives are to improve drug release of CASS and assess safety and pharmacokinetics in rabbits. METHODS: Dip coating was used to create the CASS with 2 mg ciprofloxacin and 5 mg azithromycin. A uniformed double coating was assessed with scanning electron microscopy (SEM), and the release patterns of both drugs and lactate dehydrogenase (LDH) assay were evaluated over 14 days in vitro...

In clinical trials, unilateral or bilateral data can usually be encountered if a subject contributes one or both of paired organs. For the bilateral data, responses from two paired body parts are correlated. In this paper, we study various confidence intervals of common risk difference in stratified unilateral and bilateral data based on the Dallal's model. Simulation results show that the score method outperforms other methods and provides coverage probability close to the nominal level and satisfactory coverage width...

Oral sub-mucous fibrosis (OSMF) is a severe crippling malignant disorder which affects the oral mucosa. The transforming growth factor beta (TGF-β) is one of the cytokines involved with the cell proliferation, cell growth and apoptosis. Several traditional and synthetic medications have been tried in OSMF. This study attempts to identify the FDA approved drugs (including both synthetic and herbal medications) with least side effects, highest efficacy and robust dynamic mechanism for the treatment of OSMF...

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)...

The over-the-counter nasal decongestant oxymetazoline (eg, Afrin) is used in the pediatric population for a variety of conditions in the operating room setting. Given its vasoconstrictive properties, it can have cardiovascular adverse effects when systemically absorbed. There have been several reports of cardiac and respiratory complications related to use of oxymetazoline in the pediatric population. Current US Food and Drug Administration approval for oxymetazoline is for patients ≥6 years of age, but medical professionals may elect to use it short-term and off label for younger children in particular clinical scenarios in which the potential benefit may outweigh risks (eg, active bleeding, acute respiratory distress from nasal obstruction, acute complicated sinusitis, improved surgical visualization, nasal decongestion for scope examination, other conditions, etc)...

HYPOTHESIS: AR42, a histone deacetylase (HDAC) inhibitor, reduces viability of primary vestibular schwannoma (VS) cells and delays tumor progression and hearing loss (HL) in a xenograft model of VS. BACKGROUND: The impact of HDAC expression on AR42 response in primary VS cells is unknown, as well as the effects of AR42 on VS-associated HL and imbalance. METHODS: Primary human VS cells (n = 7) were treated with AR42 (0-3.0 μM), and viability assays were conducted...

Objectives: Two pilot studies of AR-42, a pan-histone deacetylase inhibitor, in human neurofibromatosis type 2 (NF2), vestibular schwannomas (VS), and meningiomas are presented. Primary endpoints included safety, and intra-tumoral pharmacokinetics (PK) and pharmacodynamics (PD). Methods: Pilot 1 is a subset analysis of a phase 1 study of AR-42 in solid tumors, which included NF2 or sporadic meningiomas. Tumor volumes and treatment-related adverse events (TRAEs) are reported (NCT01129193)...

The over-the-counter nasal decongestant oxymetazoline (eg, Afrin) is used in the pediatric population for a variety of conditions in the operating room setting. Given its vasoconstrictive properties, it can have cardiovascular adverse effects when systemically absorbed. There have been several reports of cardiac and respiratory complications related to use of oxymetazoline in the pediatric population. Current US Food and Drug Administration approval for oxymetazoline is for patients ≥6 years of age, but medical professionals may elect to use it short-term and off label for younger children in particular clinical scenarios in which the potential benefit may outweigh risks (eg, active bleeding, acute respiratory distress from nasal obstruction, acute complicated sinusitis, improved surgical visualization, nasal decongestion for scope examination, other conditions, etc)...

BACKGROUND: There are significant drug-drug interactions between human immunodeficiency virus antiretroviral therapy and intranasal steroids, leading to high serum concentrations of iatrogenic steroids and subsequently Cushing's syndrome. METHOD: All articles in the literature on cases of intranasal steroid and antiretroviral therapy interactions were reviewed. Full-length manuscripts were analysed and the relevant data were extracted. RESULTS: A literature search and further cross-referencing yielded a total of seven reports on drug-drug interactions of intranasal corticosteroids and human immunodeficiency virus protease inhibitors, published between 1999 and 2019...

Optimal management of airplane headache (AH) is still unresolved. A female, 53 years, complained of severe short-lasting jabbing pain attacks over the forehead and in the eyebrows, mainly on the left side, that occur during take-off and landing. Neurological, opthalmological, and otolaryngological examinations and brain MRI were normal. It was diagnosed as AH. The patient was recommended to take 10 mg rizatriptan 30 min before the flight. It resulted in a complete absence of headache during the take-off and significant decrease of pain intensity during the plane descending...

OBJECTIVE: To evaluate local and systemic safety of bilateral iontophoretic administration of lidocaine with epinephrine or lidocaine alone to the tympanic membrane (TM). STUDY DESIGN: A randomized, double-blind, two-arm study was conducted at a single center. Healthy adults were randomized to bilateral iontophoretic treatment with 2% lidocaine, 1:100,000 epinephrine, or 2% lidocaine (control). Otoscopy, cranial nerve examination, tympanometry, and audiometry safety evaluations were conducted before and 3-days post-procedure...

Intra-cochlear fibrous tissue formation around the electrode following cochlear implantation affects the electrode impedance as well as electrode explantation during reimplantation surgeries. Applying corticosteroids in cochlear implantation is one way of minimizing the intra-cochlear fibrous tissue formation around the electrode. It were J. Kiefer, C. von Ilberg, and W. Gstöttner who proposed the first idea on drug delivery application in cochlear implantation to MED-EL in the year 2000. During the twenty years of translational research efforts at MED-EL in collaboration with several clinics and research institutions from across the world, preclinical safety and efficacy of corticosteroids were performed leading to the final formulation of the electrode design...

OBJECTIVES: To determine safety, feasibility, and preliminary activity of transtympanic injection of sodium thiosulfate (STS) against cisplatin-induced hearing loss (CIHL).DESIGN Randomized controlled trial.SETTING Tertiary cancer hospital.PATIENTS Adults to be treated with high-dose cisplatin (≥ 75 mg/m2).INTERVENTION Selected by randomization, 0.1 M STS gel on one side and placebo gel on the other side was transtympanically applied to the middle ear 3 hours before cisplatin administration...

OBJECTIVES: There are no approved pharmacologic therapies for chronic sensorineural hearing loss (SNHL). The combination of CHIR99021+valproic acid (CV, FX-322) has been shown to regenerate mammalian cochlear hair cells ex vivo. The objectives were to characterize the cochlear pharmacokinetic profile of CV in guinea pigs, then measure FX-322 in human perilymph samples, and finally assess safety and audiometric effects of FX-322 in humans with chronic SNHL. STUDY DESIGNS: Middle ear residence, cochlear distribution, and elimination profiles of FX-322 were assessed in guinea pigs...

In a phase IIb clinical study (dose-finding test, 450 mg dosing group: 150 mg t.i.d., 500 mg dosing group: 250 mg b.i.d., 900 mg dosing group: 300 mg t.i.d.) of tebipenem pivoxil (TBPM-PI) for treatment of otolaryngological infections in adults, TBPM concentrations in the patient plasma were quantified. The primary pharmacokinetic parameters such as ka, kel, Vd/F and Tlag were estimated by the Bayesian method and then the secondary pharmacokinetic parameters such as tmax, Cmax, t1/2 and AUC were calculated...

In 1999 the following guidelines were elaborated by a consensus conference of the German Society of Oto-Rhino-Laryngology, Head and Neck Surgery with delegates of 10 further societies and complemented by a Delphi procedure. In 2002 and 2008 up-dates were performed by the members of the consensus conference, the chair of the study group of ENT infectiology of the German Society of Oto-Rhino-Laryngology, Head and Neck Surgery and the presidency of the German Society of Oto-Rhino-Laryngology, Head and Neck Surgery...

Tebipenem pivoxil (TBPM-PI, ME1211) has been under development as the world's first oral carbapenem for treatment of otolaryngological/respiratory infections caused by drug-resistant S. pneumoniae in pediatric patients. In order to treat these infections effectively, it is important to design optimal dosing regimens based on the pharmacokinetics/pharmacodynamics (PK/PD) relationships, which can be characterized by clarifying the pharmacokinetics of tebipenem (TBPM) in the pediatric population. We therefore performed an population pharmacokinetic analysis using plasma TBPM concentrations obtained from pediatric patients with otolaryngological infection or bacterial pneumonia (0...

There are many types of pain induced in otolaryngology, stemming from medical acts, sinus drainage, packing of the nasal fossae, or complex bandaging after cancer surgery. In patients with impaired communication abilities resulting from impaired speech, greater attention must be paid to induced pain, sometimes requiring the use of behavioral evaluation scales. Preventing this pain means organizing medical acts and painful treatments by attempting to group them and informing the patient that the caregiver is listening to him and relieving his pain...

OBJECTIVE: Describe the pharmacokinetics of ciprofloxacin and dexamethasone after administration of CIPRODEX Otic Suspension (CIP/DEX) into the middle ears of children. DESIGN: Open-label, single-dose, pharmacokinetic studies, administering four drops of CIP/DEX instilled into each middle ear through the tympanostomy tubes immediately following tube placement. Blood was collected for 6h and analyzed for ciprofloxacin and dexamethasone concentrations using a validated liquid chromatography and tandem mass spectrometry (LC/MS/MS) method...

The antibiotic preferences of 2,190 pediatricians (peds) 360 general practitioners (GPs), and 273 otolaryngologists (ENTs) in the United States and concurrence with treatment guideline recommendations for acute otitis media (AOM) for suspected drug-resistant Streptococcus pneumoniae (DRSP) and beta-lactamase-producing Haemophilus influenzae before and after an educational workshop were compared. Peds and GPs preferred amoxicillin/clavulanate high-dose, whereas ENTs preferred higher generation cephalosporins...