True Nasopharyngeal Absorption of Zolmitriptan after Administration via Nasal Spray in Healthy Male Volunteers

Kågedal, Matts; Zingmark, Per-Henrik; Hedlund, Cecilia; Yates, Roger

doi:10.2165/00137696-200503020-00005

Cited by 12 publications

(24 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…30,31 These triptan conventional nasal sprays display a bimodal absorption pattern with a fairly small early peak attributed predominantly to absorption across the nasal mucosa, followed by a later more distinct peak representing GI absorption of the significant amount of drug swallowed after bypassing the nose. [30][31][32][33] For zolmitriptan, the nasal fraction has been quantified in a study and found to account for approximately 30% of the total absorption. 32 A similar study has not been conducted with sumatriptan nasal spray, though sumatriptan liquid nasal spray pharmacokinetics have been studied.…”

Section: Nasal Delivery Of Headache Medicationsmentioning

confidence: 99%

“…[30][31][32][33] For zolmitriptan, the nasal fraction has been quantified in a study and found to account for approximately 30% of the total absorption. 32 A similar study has not been conducted with sumatriptan nasal spray, though sumatriptan liquid nasal spray pharmacokinetics have been studied. 31,33 It is important to note that the approved dose of zolmitriptan delivered nasally is the same as the highest dose for tablets (5 mg), whereas the range of approved conventional sumatriptan nasal spray doses (5, 10, and 20 mg) is fivefold lower than the oral doses (25, 50, and 100 mg).…”

Section: Nasal Delivery Of Headache Medicationsmentioning

confidence: 99%

See 1 more Smart Citation

Breath Powered Nasal Delivery: A New Route to Rapid Headache Relief

2013

View full text Add to dashboard Cite

The nose offers an attractive noninvasive alternative for drug delivery. Nasal anatomy, with a large mucosal surface area and high vascularity, allows for rapid systemic absorption and other potential benefits. However, the complex nasal geometry, including the narrow anterior valve, poses a serious challenge to efficient drug delivery. This barrier, plus the inherent limitations of traditional nasal delivery mechanisms, has precluded achievement of the full potential of nasal delivery. Breath Powered bi-directional delivery, a simple but novel nasal delivery mechanism, overcomes these barriers. This innovative mechanism has now been applied to the delivery of sumatriptan. Multiple studies of drug deposition, including comparisons of traditional nasal sprays to Breath Powered delivery, demonstrate significantly improved deposition to superior and posterior intranasal target sites beyond the nasal valve. Pharmacokinetic studies in both healthy subjects and migraineurs suggest that improved deposition of sumatriptan translates into improved absorption and pharmacokinetics. Importantly, the absorption profile is shifted toward a more pronounced early peak, representing nasal absorption, with a reduced late peak, representing predominantly gastrointestinal (GI) absorption. The flattening and “spreading out” of the GI peak appears more pronounced in migraine sufferers than healthy volunteers, likely reflecting impaired GI absorption described in migraineurs. In replicated clinical trials, Breath Powered delivery of low-dose sumatriptan was well accepted and well tolerated by patients, and onset of pain relief was faster than generally reported in previous trials with noninjectable triptans. Interestingly, Breath Powered delivery also allows for the potential of headache-targeted medications to be better delivered to the trigeminal nerve and the sphenopalatine ganglion, potentially improving treatment of various types of headache. In brief, Breath Powered bi-directional intranasal delivery offers a new and more efficient mechanism for nasal drug delivery, providing an attractive option for improved treatment of headaches by enabling or enhancing the benefits of current and future headache therapies.

show abstract

Section: Nasal Delivery Of Headache Medicationsmentioning

confidence: 99%

Section: Nasal Delivery Of Headache Medicationsmentioning

confidence: 99%

Breath Powered Nasal Delivery: A New Route to Rapid Headache Relief

2013

View full text Add to dashboard Cite

show abstract

“…By giving oral-activated charcoal, which can block drug absorption in GI, the direct absorption of zolmitriptan through nasal mucosa after administration via nasal spray was found to contribute only 29% of total zolmitriptan exposure. After intranasal administration of zolmitriptan, it was found that there was 30% of the total dose converted to 183C91, its active metabolite, via GI metabolism, whereas no zolmitriptan or 183C91 was detected in patients with charcoal treatment after ingestion of zolmitriptan tablet (28). Through similar strategy, the actual nasal absorption of beclomethasone dipropionate was suggested to be less than 1% after intranasal dosing.…”

Section: Contribution Of Gi Absorption and Metabolism After Intranasamentioning

confidence: 99%

Intranasal Delivery—Modification of Drug Metabolism and Brain Disposition

Wong

Zuo

2010

Pharm Res

View full text Add to dashboard Cite

Intranasal route continues to be one of the main focuses of drug delivery research. Although it is generally perceived that the nasal route could avoid the first-pass metabolism in liver and gastrointestinal tract, the role of metabolic conversions in systemic and brain-targeted deliveries of the parent compounds and their metabolites should not be underestimated. In this commentary, metabolite formations after intranasal and other routes of administration are compared. Also, the disposition of metabolites in plasma and brain after nasal administrations of parent drugs, prodrugs and preformed metabolites will be discussed. The importance and implications of metabolism for future nasal drug development are highlighted.

show abstract

“…15 A clinical pharmacology study in adults that was designed to delineate oral from intranasal absorption of ZNS suggested that intranasal absorption, although only responsible for 28.7% of total zolmitriptan absorption, contributed to 70.8% of zolmitriptan exposure during the first hour after ZNS administration. 16 The recommended starting dose for ZNS in adults and pediatric patients 12 years of age and older is 2.5 mg, and the maximum recommended single dose of zolmitriptan is 5 mg. 1,17 Zolmitriptan has low protein binding of ß25%. 18 Bioavailability of zolmitriptan is about 42% for nasal spray and 40%-48% for oral formulations 19 and is rapidly absorbed, with a median time to peak concentration (T max ) of 2-4 hours in plasma for the ZNS 16,18 and a half-life of approximately 3 hours.…”

mentioning

confidence: 99%

“…16 The recommended starting dose for ZNS in adults and pediatric patients 12 years of age and older is 2.5 mg, and the maximum recommended single dose of zolmitriptan is 5 mg. 1,17 Zolmitriptan has low protein binding of ß25%. 18 Bioavailability of zolmitriptan is about 42% for nasal spray and 40%-48% for oral formulations 19 and is rapidly absorbed, with a median time to peak concentration (T max ) of 2-4 hours in plasma for the ZNS 16,18 and a half-life of approximately 3 hours. 18,19 Dose proportionality was demonstrated for the plasma area under the curve (AUC) and maximum concentration (C max ) for both zolmitriptan and the active N-desmethyl metabolite (183C91) in adults following administration of single and multiple doses of 0.5, 1, 2.5, and 5 mg ZNS.…”

mentioning

confidence: 99%

Population Pharmacokinetic Analysis of Zolmitriptan and Its Metabolite in Adults and Adolescents to Support Dose Selection in Children With Migraine

Zhou

Birmingham

et al. 2017

The Journal of Clinical Pharma

View full text Add to dashboard Cite

Zolmitriptan is a serotonin (5-HT) receptor agonist effective for the treatment of migraine. This analysis aimed to develop a population pharmacokinetic (PK) model for zolmitriptan and its active metabolite in adults and adolescents and provide appropriate dosing regimens to be used in clinical trials for children 6-11 yearsold. The data from a single-dose clinical study of 5.0-mg zolmitriptan nasal spray (ZNS) conducted in adult and adolescent patients with migraine between migraine attacks was applied. Similar plasma concentration profiles of zolmitriptan and its metabolite, 183C91, were observed in adults and adolescents. A 1-compartment model with first-order absorption and first-order elimination reasonably described the zolmitriptan PK. With a portion of elimination of zolmitriptan being treated as the conversion from zolmitriptan to 183C91, the disposition of 183C91 was described by a 1-compartment model with first-order elimination. The estimated typical apparent volume of distribution and clearance of zolmitriptan were 136 L and 121 L/h, respectively, with 56.5% and 42.6% between-subject variability, respectively. Based on the simulation results with the final population PK model, a body weight-based dosing scheme of 5.0 and 2.5 mg ZNS in children greater than and less than 50 kg is recommended to achieve exposures similar to those of the adult and adolescent population administered 5.0 mg ZNS. The recommended doses for children to achieve exposure similar to that observed in adults given 2.5 mg ZNS are 2.5 mg (≥50 kg) and 1.0 mg (15-50 kg). These dosing regimens could be used in future clinical trials.

show abstract

True Nasopharyngeal Absorption of Zolmitriptan after Administration via Nasal Spray in Healthy Male Volunteers

Cited by 12 publications

References 12 publications

Breath Powered Nasal Delivery: A New Route to Rapid Headache Relief

Breath Powered Nasal Delivery: A New Route to Rapid Headache Relief

Intranasal Delivery—Modification of Drug Metabolism and Brain Disposition

Population Pharmacokinetic Analysis of Zolmitriptan and Its Metabolite in Adults and Adolescents to Support Dose Selection in Children With Migraine

Contact Info

Product

Resources

About