xylometazoline hydrochloride [keywords]
- Cloud-point extraction is compatible with liquid chromatography coupled to electrospray ionization mass spectrometry for the determination of antazoline in human plasma. [Journal Article]
- J Pharm Biomed Anal 2016 Sep 5.:294-301.
Cloud-point extraction (CPE) is attracting increasing interest in a number of analytical fields, including bioanalysis, as it provides a simple, safe and environmentally-friendly sample preparation technique. However, there are only few reports on the application of this extraction technique in liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) analysis. In this study, CPE was used for the isolation of antazoline from human plasma. To date, only one method of antazoline isolation from plasma exists-liquid-liquid extraction (LLE). The aim of this study was to prove the compatibility of CPE and LC-ESI-MS/MS and the applicability of CPE to the determination of antazoline in spiked human plasma and clinical samples. Antazoline was isolated from human plasma using Triton X-114 as a surfactant. Xylometazoline was used as an internal standard. NaOH concentration, temperature and Triton X-114 concentration were optimized. The absolute matrix effect was carefully investigated. All validation experiments met international acceptance criteria and no significant relative matrix effect was observed. The compatibility of CPE and LC-ESI-MS/MS was confirmed using clinical plasma samples. The determination of antazoline concentration in human plasma in the range 10-2500ngmL(-1) by the CPE method led to results which are equivalent to those obtained by the widely used liquid-liquid extraction method.
- Application of a novel liquid chromatography/tandem mass spectrometry method for the determination of antazoline in human plasma: Result of ELEPHANT-I [ELEctrophysiological, pharmacokinetic and hemodynamic effects of PHenazolinum (ANTazoline mesylate)] human pharmacokinetic study. [Journal Article, Research Support, Non-U.S. Gov't]
- J Pharm Biomed Anal 2016 May 10.:113-9.
Antazoline is a first-generation antihistaminic agent with antiarrhythmic quinidine-like properties. In some countries, it is widely used for termination of cardiac arrhythmias, especially atrial fibrillation (AF). However, no human pharmacokinetic studies have been conducted with intravenous antazoline. The aim of our study was to develop and validate a novel liquid chromatography/tandem mass spectrometry (LC-MS/MS) method for the determination of antazoline in human plasma: the ELEPHANT-I [ELEctrophysiological, pharmacokinetic and hemodynamic effects of PHenazolinum (ANTazoline mesylate)] human pharmacokinetic study. Antazoline was extracted from plasma using liquid-liquid extraction. The concentration of the analyte was measured by LC-MS/MS with xylometazoline as an internal standard. The method was validated for linearity, precision, accuracy, stability (freeze/thaw stability, stability in autosampler, short and long term stability), dilution integrity and matrix effect. The analyzed validation criteria were fulfilled. The method was applied to a pharmacokinetic study involving 10 healthy volunteers. Following a single intravenous dose of antazoline mesylate (100 mg), the plasma concentration profile showed a relative fast elimination with a terminal elimination half-life of 2.29 h. A relatively high volume of distribution was observed (Vss=315 L). The values of mean residence time (MRT∞), area under the curve (AUC∞) and clearance were 3.45 h, 0.91 mg h L(-1) and 80.5 L h(-1), respectively. One volunteer showed significant differences in pharmacokinetic parameters. In conclusion, the proposed new LC-MS/MS method was successfully used for the first time for the determination of antazoline in human plasma.
- Assessment of maternal drug intake by urinary bio monitoring during pregnancy and postpartally until the third perinatal year. [Journal Article]
- Pharmacoepidemiol Drug Saf 2016 Apr; 25(4):431-7.
Although sales of prescribed and over-the-counter (OTC) medication are rising, little is known about individual drug intake. This study was aimed to obtain complementary information about drug intake.Information on drug utilization was obtained in a female cohort for five different time points (TP): 36th week of pregnancy (n = 622), 7th perinatal week (n = 533), 3rd perinatal month (n = 340), and 1st perinatal (n = 534) and 3rd perinatal year (n = 324) by a validated urine screening method.Drugs were detected 807 times among all analyzed samples (n = 2353) with less drug intake for early TP compared with later TP (~24.4%, n = 152; ~33.8%, n = 180; ~23.2%, n = 79; ~42.5%, n = 227; and ~52.2%, n = 169). The diversity of drugs increased from 25 up to 40 different drugs for the investigated period. OTC drugs were detected most frequently reflected by the top three drugs: acetaminophen (~37%, n = 292), ibuprofen (~23%, n = 183), and xylometazoline (~12%, n = 98). Mainly guideline-orientated drug therapy was observed. However, contraindicated ibuprofen intake during third trimester urine samples (n = 26) and a repeated usage of acetaminophen and/or ibuprofen (n = 9), as well as xylometazoline (n = 7), reveal missing information about drug safety.Bio monitoring was applied for detection of drug intake revealing a lack of information about OTC products and their health risks. Hence, information about health risks for certain drugs and patient groups must be improved for and by pharmacists, to avoid (i) usage of contraindicated drugs and (ii) abuse of OTC drugs.
- [Local anesthesia in the children undergoing the fibroendoscopic study of the nasal cavity, nasopharynx, and larynx: are topical anesthetics needed?]. [English Abstract, Journal Article, Randomized Controlled Trial]
- Vestn Otorinolaringol 2015; 80(5):51-5.
This prospective randomized study with double blind control was designed to evaluate the effectiveness of various anesthetic techniques employed prior to fibroendoscopy of the nose, nasopharynx, and larynx of the children. The study included 160 children at the age varying from 3 to 14 (mean 7.4±2.96) years randomly allocated to four statistically comparable groups matched for age and sex. The following preparations were used to treat the children prior to fibroendoscopy: physiological solution (group 1), a 0.05% xylometazoline solution (group 2), a 10% lidocaine solution (group 3), and a mixture of 0.05% xylometazoline and 10% lidocaine solutions (group 4). The evaluation of the tolerance to the pretreatment of the nasal cavity with lidocaine and lidocaine plus xylometazoline (groups 3 and 4) showed that it was significantly (p<0.05) worse than in groups 1 and 2. The subjective tolerance to fibroendoscopy as reported by the patients was on the average similar in the children of all four groups (p>0.05). The doctors found the tolerance of fibroendoscopy to be the worst following pretreatment with the physiological solution (group 1) and the best after pretreatment with a mixture of lidocaine and xylometazoline (group 4) (p=0.03). The children comprising groups 2 and 3 were not significantly different in terms of the tolerance to fibroendoscopy (p>0.05). It is concluded that the pretreatment of the nasal cavity of the children with a 10% lidocaine solution before fibroendoscopy has no advantage over the pretreatment with a 0.05% xylometazoline solution; at the same time, insuflation of lidocaine as an anesthetic induces more pronounced negative emotions compared with the application of 0.05% xylometazoline.
- Four-phase rhinomanometry: a multicentric retrospective analysis of 36,563 clinical measurements. [Journal Article]
- Eur Arch Otorhinolaryngol 2016 May; 273(5):1185-98.
Rhinomanometry can still be considered as the standard technique for the objective assessment of the ventilatory function of the nose. Reliable technical requirements are given by fast digital sensors and modern information technology. However, the xyimaging of the pressure-flow relation typically shows loops as a sign of hysteresis, with the need for resolution of the breath in four phases. The three pillars of 4-phase rhinomanometry (4PR) are the replacement of estimations by measurements, the introduction of parameters related to the subjective sensing of obstruction, and the graphical information regarding the disturbed function of the nasal valve. In a meta-analysis of 36,563 clinical measurements, we analyze the errors of the "classic" parameters (flow in 150 Pa) and reject the further use of these parameters as obsolete, because they correspond to an inaccurate estimation rather than proper measurement. In a pre-study of 1580 measurements, the logarithmic effective resistance (Reff) was found to have the highest correlation with values obtained from a visual analog scale. Next, we classify the inspiratory effective resistance in 20,069 measurements without treatment and 16,494 measurements after decongestion with xylometazoline 0.1 % spray in 20 % percentiles. The gradation of obstruction delivers not only "normal" values but also indications for the severity of the obstruction in adult Caucasian noses. Adoption of the distribution for the growing nose and analysis of the total nasal resistance is addressed, and typical findings of nasal valve phenomena are outlined.
- Effectiveness of conservative treatment in the management of secretory otitis media. [Journal Article]
- J Ayub Med Coll Abbottabad 2014 Jul-Sep; 26(3):337-40.
Secretory otitis media is a very important and common ENT disease, especially in the children. The aetiology of Secretory otitis media is multifocal, and the treatment is initially medical or conservative and if it fails then surgery is indicated. The objective of the study was to determine the efficacy of medical treatment in the management of Secretory otitis media.This cross sectional descriptive study was conducted at the outpatient department of ENT, Ayub Medical Institute (AMI) Abbottabad, from Mar to Sep 2013. A total of 40 patients were included in this study and standard medical treatment of secretory otitis media was given. The patients were followed up at 2nd and then 4th week and results were analysed.Both clinical and audiological diagnosis of secretory otitis media was made and patients were followed up at 2nd and 4th week to see the effect of treatment. Among 40 patients, 26 (65%) completely recovered from the disease while 14 patients (35%) did not improve.Conservative treatment is effective in the management of Secretory otitis media.
- Impact of xylomethazoline on eustachian tube function in healthy participants. [Journal Article]
- Otol Neurotol 2015 Jun; 36(5):769-75.
The use of decongestants is common in otitis media eustachian tube (ET) dysfunction. However, the underlying mechanism and the type of action on the complex middle ear pressure equalization system are poorly understood. Here, by use of the pressure chamber, we investigated the impact of intranasal decongestive therapy (xylomethazoline) on ET function.Thirty healthy participants (60 ears) were exposed to a predetermined profile of phases of compression and decompression in a hypobaric and hyperbaric pressure chamber. ET opening pressure, ET opening duration, ET opening frequency, and ET closing pressure were determined before and after intranasal application of xylomethazoline.A significantly higher number of ET openings (ET opening frequency) in passive equalization condition could be measured after application of decongestants than before. No significant difference could be found in the values of ET opening pressure, ET opening duration, and ET closing pressure parameters before in comparison with the values after application of xylomethazoline.We conclude that xylomethazoline might only have a minor effect during active and passive middle ear pressure equalization. Larger cohorts and targeted application of decongestants should be tested to confirm these preliminary data and to find new evidence on the effects of decongestants.
- [Ciliary epithelium and topical decongestants: how to minimize the undesirable events?]. [English Abstract, Journal Article]
- Vestn Otorinolaringol 2014; (5):76-9.
The objective of the present study was to evaluate the influence of the combination of 0.1% xylometazoline with seawater (Rinomaris, "Jadran", Croatia) on the state and functional activity of the ciliary epithelium of the nasal cavity. The results of the study confirm the safety of this treatment and the possibility of its application in routine clinical practice.
- A pilot study assessing tolerance safety and feasibility of diagnostic transnasal esophagogastroduodenoscopy using an improved larger caliber endoscope and an adapted topical anesthesia. [Journal Article]
- Surg Endosc 2015 Oct; 29(10):3002-9.
Transnasal esophagogastroduodenoscopy (TN-EGDS) is well tolerated by patients and the examination is perceived comfortable without the need of a sedative drug. Conversely, mainly in Western literature, some authors report limitations in illumination, image quality, and working channel as affecting TN-EGDS diffusion. To overcome these disadvantages, a new transnasal endoscope (TNE) was tested but, due to its larger diameter, we have no evidence of its clinical safety and tolerability. A new adapted nasal anesthesia could be useful to improve TNE tolerance. In an independent, not sponsored, pilot prospective study we enrolled, in a busy clinical hospital setting, 30 adult patients receiving nasal atomized Lidocaine and Xylometazoline (XAL) to undergo a diagnostic TN-EGDS with TNE to evaluate its tolerance, safety, and feasibility.Three physicians enrolled inpatients and outpatients with indication to diagnostic EGDS during a 6-month period. Main outcome measures were cardio-pulmonary monitoring data and patients' answers to an adapted questionnaire investigating pain, anxiety level, willingness to repeat the examination, operators' scores about endoscopy quality, examination conduction and anesthesia-related complications.The examination was completed by the transnasal route in 100 % of the enrolled patients, endoscopy satisfaction and feasibility were scored to nearly the highest levels by the three different physicians. A total of 29/30 patients (96.6 %) declared the willingness to repeat the same examination if needed. The mean patients' score for overall pain was 3.7 ± 1 SD (range 1-10 by Visual Analog Scale). Mean endoscopy duration was 11.1 ± 2.6 min (range 5.0-19.0). In a total of 17/30 TN-EGDS that lasted more than 11 min, higher heart frequency variations and worse tolerance scores were found (p < 0.05).Our pilot study demonstrates that TN-EGDS with TNE and NA is safe, well tolerated, and feasible. The best clinical tolerance is reached when TN-EGDS lasts <11 min.
- Anti-allergic effect of intranasal administration of type-A procyanidin polyphenols based standardized extract of cinnamon bark in ovalbumin sensitized BALB/c mice. [Journal Article, Research Support, Non-U.S. Gov't]
- Phytother Res 2015 Mar; 29(3):423-33.
The objective of the present work was to evaluate anti-allergic effects of intranasal administration of type-A procynidines polyphenols (TAPP) based standardized hydroalcoholic extract of Cinnamomum zeylanicum bark (TAPP-CZ) in ovalbumin (OVA)-induced experimental allergic rhinitis (AR) in BALB/c mice. Sixty male BALB/c mice were divided into six groups of ten each (G1-G6). The mice from G1 were nonsensitized and maintained as normal group. Remaining mice (G2-G6) were sensitized with OVA (500 μL solution, intraperitoneal) on alternate days for 13 days and had twice daily intranasal treatment from day 14-21 as follows: G2 (AR control) received saline, G3 (positive control, XLY) received xylometazoline (0.5 mg/mL, 20 μL/nostril) and G4-G6 received TAPP-CZ (3, 10 and 30 µg/kg in nostril), respectively. On day 21, mice were challenged with OVA (5 μL/nostril, 5% solution) and assessments (nasal signs, biochemical and histopathological) were performed. Treatment with TAPP-CZ (10 and 30 µg/kg in nostril) showed significant attenuation in OVA-induced alterations of the nasal (number of nasal rubbing and sneezing), biochemical markers (serum IgE and histamine), haematological, morphological (relative organ weight of spleen and lung) and histopathological (nasal mucosa and spleen) parameters. In conclusion, TAPP-CZ showed anti-allergic efficacy in animal model of AR.