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

Dingemanse, Jasper; Soubrouillard, C; Paris, J.; Pisano, Pascale; Blin, Olivier

doi:10.1067/mcp.2000.108196

Cited by 9 publications

(7 citation statements)

References 18 publications

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“…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.…”

Section: Discussionsupporting

confidence: 81%

“…There was a tendency towards a higher frequency of these adverse events in the 4 and 6 mg dose groups. These results confirm those obtained in a previous study [13].…”

Section: Tolerabilitysupporting

confidence: 83%

“…CCM is a mixture of monoesters, diesters and triesters of glycerol, and monoesters and diesters of macrogols, with a mean relative molecular mass between 200 and 400 [12]. In the presence of CCM, the extent of absorption of IS-159has been shown to be markedly increased'without change in the time to reach the maximum plasma concentration and the elimination half-life [13]. The fast absorption of IS-159 after nasal application may lead to an efficacy profile that resembles that of subcutaneous surnatriptan, i.e., a fast onset of action, but without the need for injection.…”

Section: Is-159mentioning

confidence: 99%

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

Giersbergen¹,

Dingemanse²

2003

Eur. J. Drug Metab. Pharmacokinet.

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This study was designed to investigate the multiple-dose pharmacokinetics of a range of intransal doses of IS-159, a serotonin 1B/1D receptor agonist. Intranasal doses of 1, 2, 4 and 6 mg of IS-159 were administered twice at an interval of 4 hours to 17 healthy male and female subjects in a two-way crossover study. Plasma concentrations of IS-159 were determined from blood samples taken at regular intervals up to 24 hours after the first administration during both treatment periods. IS-159 was rapidly absorbed and eliminated with a t(max) of approximately 15 min and a t(1/2) of approximately 1.6 hours. With increasing dose, the exposure increased dose-proportionally, and IS-159 pharmacokinetics appear not to be influenced by gender and food intake. The results showed dose-proportional pharmacokinetics of IS-159 in the dose range tested and a low propensity for drug accumulation.

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Section: Discussionsupporting

confidence: 81%

“…There was a tendency towards a higher frequency of these adverse events in the 4 and 6 mg dose groups. These results confirm those obtained in a previous study [13].…”

Section: Tolerabilitysupporting

confidence: 83%

Section: Is-159mentioning

confidence: 99%

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

Giersbergen¹,

Dingemanse²

2003

Eur. J. Drug Metab. Pharmacokinet.

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“…A score of 10 was considered the least tolerable. This scale is analogous to Visual Analog Scales and has been adapted from a previous study evaluating the tolerability of a nasal formulation (11). Subjects also completed a pain and subjective discomfort questionnaire for the i.n.…”

Section: Methodsmentioning

confidence: 99%

Pharmacokinetics and tolerability of intranasal diazepam and midazolam in healthy adult volunteers

Ivaturi

Riss²,

Kriel

et al. 2009

Acta Neurologica Scandinavica

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Objective – The purpose of this pilot study was to determine the pharmacokinetics and tolerability of an investigational diazepam (DZP) formulation and a parenteral midazolam (MDZ) formulation following intranasal (i.n.) administration for the efficient treatment of seizure emergencies. Methods – Each subject received 5 mg of DZP and MDZ via both i.n. and intravenous routes in a four‐way, randomized crossover trial. Blood samples were collected over 48 h. DZP and MDZ concentrations were measured using HPLC. Using analog scales, subjects rated tolerability (0 = no change from normal; 10 = maximum intolerability) and pain (0 = no pain; 4 = extreme pain) prior to and 0, 5, 15, 60 min, and 8 h after administration. Results – The Cmax and Tmax values for i.n. DZP and MDZ were 179.2 ng/ml and 28.8 min vs 62.8 ng/ml and 21.6 min, respectively. Immediately following i.n. administration, subjects reported tolerability scores of 6.75 and 6.0, and identical pain scores, 3.2, for DZP and MDZ, respectively. Conclusion – Both formulations were rapidly absorbed following i.n. administration with transient discomfort. DZP had a longer half‐life, which may result in an extended duration of action. Further studies in large patient populations to evaluate the safety after long term use, efficacy and pharmacokinetics of i.n. DZP are warranted.

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“…Enhanced absorption might be achieved using positively charged liposomes, which confer a bioadhesive effect on the negatively charged nasal mucosa [102]. Furthermore, intranasal peptide delivery might be markedly increased by caprylocaproyl macrogolgycerides by enhancing absorption through the nasal mucosa [103].…”

Section: Intranasal Drug Deliverymentioning

confidence: 99%

Stroke, dementia, and drug delivery

Ford¹,

Bryant

Mangoni

et al. 2003

Brit J Clinical Pharma

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Stroke and dementia represent a major health burden for elderly subjects as they are associated with significant morbidity and mortality. The rates of stroke and dementia are progressively increasing due to the ageing population in most westernized countries. Therefore, both these conditions represent a major therapeutic target. However, the therapeutic options available for the management of stroke and dementia remain largely unsatisfactory, the main reason being the difficulty in transferring the results obtained in animal and in vitro studies to the clinical setting. This review focuses on the recent advances in pathophysiology and treatment of these conditions and future directions for research. Moreover, the technique of functional magnetic resonance imaging is discussed in detail as a tool to assess the effects of therapeutic agents on the central nervous system and monitor the prog ression of diseases. Finally, an overview of the issue of drug delivery into the central nervous system is presented. Stroke (G. A. Ford)Stroke is a key therapeutic target because it is the leading cause of severe disability and third highest cause of death in developed countries. Over 75% of patients are aged ≥ 65 years. In 85-90% of cases stroke is due to cerebral infarction. Important advances have been made in establishing benefits of lowering blood pressure and serum cholesterol as well as in antiplatelet drug therapy in primary and secondary stroke prevention [1,2]. This review focuses on acute management within the first

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

Abstract: 2% caprylocaproyl macrogolglyceride markedly increased the absorption of IS-159 through the nasal mucosa and elicited only mild irritant effects.

Cited by 9 publications

References 18 publications

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

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

Pharmacokinetics and tolerability of intranasal diazepam and midazolam in healthy adult volunteers

Stroke, dementia, and drug delivery

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