The Use of a Radiolabelled Saccharin Solution to Monitor the Effect of the Preservatives Thiomersal, Benzalkonium Chloride and EDTA on Human Nasal Clearance

Abstract

The effect of thiomersal, benzalkonium chloride and ethylenediaminetetraacetic acid (EDTA) on the nasal mucociliary clearance of healthy volunteers has been investigated using a modified saccharin test and gamma scintigraphy concomitantly. A significant correlation was found between the two techniques. Using each subject as his/her own control, none of the preservatives significantly altered the rate of clearance or proportion cleared from the nasal cavity after the administration of a single dose. This result is at variance with some in-vitro findings.

Multiple-dose pharmacokinetics of intranasally administered IS-159 in healthy subjects

“…In the presence of CCM, the absorption of 15-159 was fast, as evidenced by a median t max that ranged between 10 and 20 min for the different dose groups. This finding is in agreement with a previous study in which a value of 15 min was reported [13] and is consistent with absorption through the nasal mucosa [17]. The pharmacokinetics of alnitidan [18], an investigational5-HT 1BIl D receptor agonist, and sumatriptan [19,20] were also investigated after intranasal administration.…”

Pronounced effect of caprylocaproyl macrogolglycerides on nasal absorption of IS-159, a peptide serotonin 1B/1D-receptor agonist

“…This is consistent with absorption through the nasal mucosa in accordance with the mucociliary clearance under physiologic conditions. 20 In contrast, sumatriptan shows a t max from 1 to 1.5 hours, which reflects the fact that sumatriptan after nasal administration is swallowed to a great extent and subsequently absorbed from the gastrointestinal tract. 21,22 Nasal administration of dihydroergotamine also yields a t max of approximately 1 hour.…”

“…Blood samples of 5 mL for pharmacokinetics were collected, by means of a catheter inserted into a forearm vein, into glass tubes containing ethylenediamine tetraacetic acid as anticoagulant just before and at 5,10,15,20,25,30,35,40, and 50 minutes and at 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 10, and 12 hours after drug administration. Within 15 minutes of collection, the blood samples were spun in a centrifuge, and plasma was carefully separated.…”

Saliva oxytocin measures do not reflect peripheral plasma concentrations after intranasal oxytocin administration in men

“…This fraction is rapidly cleared to the nasopharynx within 15-30 minutes by mucociliary clearance and sni ng (Batts et al, 1991;Lansley, 1993;Weisman et al, 2012). However, a large remainder is deposited on the sparsely ciliated transitional mucosa and non-ciliated epithelium in the anterior vestibule, from where it is slowly cleared to the nasopharynx over the course of several hours (Djupesland et al, 2013;Leach et al, 2015).…”