The Experts below are selected from a list of 315 Experts worldwide ranked by ideXlab platform
Cecilia Hale - One of the best experts on this subject based on the ideXlab platform.
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A Phase I Study of the Pharmacokinetics and Pharmacodynamics of Intranasal Doxylamine in Subjects with Chronic Intermittent Sleep Impairment
Drugs in R&D, 2018Co-Authors: Mark Allison, Cecilia HaleAbstract:Introduction Doxylamine tablets are approved as an over-the-counter sleep aid. We developed a doxylamine succinate Intranasal metered-dose delivery system with the expectation of a more rapid onset of action with reduced side-effect potential compared with the oral tablet. Methods This phase I study randomized 24 adults with chronic intermittent sleep impairment to receive either single doses of Intranasal doxylamine succinate 3.2, 6.3, or 12.7 mg or doxylamine succinate 25-mg oral tablet. Doxylamine pharmacokinetics were assessed using noncompartmental methods; pharmacodynamics were evaluated using the Karolinska Sleepiness Scale (KSS) and numerous psychomotor tests. Adverse events (AEs) were monitored. Results None of the Intranasal dose levels produced a mean maximum plasma concentration ( C _max) above the 50 ng/mL target level or a time to maximum concentration shorter than that of the oral tablet. At the highest Intranasal dose, C _max and area under the doxylamine concentration–time curve were approximately 25% of the values achieved with the oral dose. Variation in most pharmacokinetic parameters was higher with Intranasal compared with oral dosing. A relationship between plasma doxylamine concentration and KSS change from baseline was evident for the 25-mg tablet and, to a lesser extent, for the 12.7-mg Intranasal dose. Changes from baseline in psychomotor parameters did not show a relationship to Intranasal dose, and did not distinguish between Intranasal versus oral dosing. The most common AEs with Intranasal dosing were nasal congestion, nasal dryness, and frontal headache. Conclusion The nasal spray did not increase doxylamine absorption or systemic bioavailability compared with the oral tablet.
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A Phase I Study of the Pharmacokinetics and Pharmacodynamics of Intranasal Doxylamine in Subjects with Chronic Intermittent Sleep Impairment.
Drugs in R&D, 2018Co-Authors: Mark Allison, Cecilia HaleAbstract:Doxylamine tablets are approved as an over-the-counter sleep aid. We developed a doxylamine succinate Intranasal metered-dose delivery system with the expectation of a more rapid onset of action with reduced side-effect potential compared with the oral tablet. This phase I study randomized 24 adults with chronic intermittent sleep impairment to receive either single doses of Intranasal doxylamine succinate 3.2, 6.3, or 12.7 mg or doxylamine succinate 25-mg oral tablet. Doxylamine pharmacokinetics were assessed using noncompartmental methods; pharmacodynamics were evaluated using the Karolinska Sleepiness Scale (KSS) and numerous psychomotor tests. Adverse events (AEs) were monitored. None of the Intranasal dose levels produced a mean maximum plasma concentration (Cmax) above the 50 ng/mL target level or a time to maximum concentration shorter than that of the oral tablet. At the highest Intranasal dose, Cmax and area under the doxylamine concentration–time curve were approximately 25% of the values achieved with the oral dose. Variation in most pharmacokinetic parameters was higher with Intranasal compared with oral dosing. A relationship between plasma doxylamine concentration and KSS change from baseline was evident for the 25-mg tablet and, to a lesser extent, for the 12.7-mg Intranasal dose. Changes from baseline in psychomotor parameters did not show a relationship to Intranasal dose, and did not distinguish between Intranasal versus oral dosing. The most common AEs with Intranasal dosing were nasal congestion, nasal dryness, and frontal headache. The nasal spray did not increase doxylamine absorption or systemic bioavailability compared with the oral tablet.
Bertrand Bellier - One of the best experts on this subject based on the ideXlab platform.
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Intranasal dna vaccination induces potent mucosal and systemic immune responses and cross protective immunity against influenza viruses
Molecular Therapy, 2011Co-Authors: Lea Torrieridramard, Benedicte Lambrecht, Helena Lage Ferreira, Thierry Van Den Berg, David Klatzmann, Bertrand BellierAbstract:The induction of potent virus-specific immune responses at mucosal surfaces where virus transmission occurs is a major challenge for vaccination strategies. In the case of influenza vaccination, this has been achieved only by Intranasal delivery of live-attenuated vaccines that otherwise pose safety problems. Here, we demonstrate that potent mucosal and systemic immune responses, both cellular and humoral, are induced by Intranasal immunization using formulated DNA. We show that formulation with the DNA carrier polyethylenimine (PEI) improved by a 1,000-fold the efficiency of gene transfer in the respiratory track following Intranasal administration of luciferase-coding DNA. Using PEI formulation, Intranasal vaccination with DNA-encoding hemagglutinin (HA) from influenza A H5N1 or (H1N1)2009 viruses induced high levels of HA-specific immunoglobulin A (IgA) antibodies that were detected in bronchoalveolar lavages (BALs) and the serum. No mucosal responses could be detected after parenteral or Intranasal immunization with naked-DNA. Furthermore, Intranasal DNA vaccination with HA from a given H5N1 virus elicited full protection against the parental strain and partial cross-protection against a distinct highly pathogenic H5N1 strain that could be improved by adding neuraminidase (NA) DNA plasmids. Our observations warrant further investigation of Intranasal DNA as an effective vaccination route.
Peter Hugo Howarth - One of the best experts on this subject based on the ideXlab platform.
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Safety and Tolerability Profiles of Intranasal Antihistamines and Intranasal Corticosteroids in the Treatment of Allergic Rhinitis
Drug Safety, 2003Co-Authors: Rami Jean Salib, Peter Hugo HowarthAbstract:Intranasal corticosteroids and Intranasal antihistamines are efficacious topical therapies in the treatment of allergic rhinitis. This review addresses their relative roles in the management of this disease, focusing on their safety and tolerability profiles. The Intranasal route of administration delivers drug directly to the target organ, thereby minimising the potential for the systemic adverse effects that may be evident with oral therapy. Furthermore, the topical route of delivery enables the use of lower doses of medication. Such therapies, predominantly available as aqueous formulations following the ban of chlorofluorocarbon propellants, have minimal local adverse effects. Intranasal application of therapy can induce sneezing in the hyper-reactive nose, and transient local irritation has been described with certain formulations. Intranasal administration of corticosteroids is associated with minor nose bleeding in a small proportion of recipients. This effect has been attributed to the vasoconstrictor activity of the corticosteroid molecules, and is considered to account for the very rare occurrence of nasal septal perforation. Nasal biopsy studies do not show any detrimental structural effects within the nasal mucosa with long-term administration of Intranasal corticosteroids. Much attention has focused on the systemic safety of Intranasal application. When administered at standard recommended therapeutic dosage, the Intranasal antihistamines do not cause significant sedation or impairment of psychomotor function, effects that would be evident when these agents are administered orally at a therapeutically relevant dosage. The systemic bioavailability of Intranasal corticosteroids varies from
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safety and tolerability profiles of Intranasal antihistamines and Intranasal corticosteroids in the treatment of allergic rhinitis
Drug Safety, 2003Co-Authors: Rami Jean Salib, Peter Hugo HowarthAbstract:Intranasal corticosteroids and Intranasal antihistamines are efficacious topical therapies in the treatment of allergic rhinitis. This review addresses their relative roles in the management of this disease, focusing on their safety and tolerability profiles. The Intranasal route of administration delivers drug directly to the target organ, thereby minimising the potential for the systemic adverse effects that may be evident with oral therapy. Furthermore, the topical route of delivery enables the use of lower doses of medication. Such therapies, predominantly available as aqueous formulations following the ban of chlorofluorocarbon propellants, have minimal local adverse effects. Intranasal application of therapy can induce sneezing in the hyper-reactive nose, and transient local irritation has been described with certain formulations. Intranasal administration of corticosteroids is associated with minor nose bleeding in a small proportion of recipients. This effect has been attributed to the vasoconstrictor activity of the corticosteroid molecules, and is considered to account for the very rare occurrence of nasal septal perforation. Nasal biopsy studies do not show any detrimental structural effects within the nasal mucosa with long-term administration of Intranasal corticosteroids. Much attention has focused on the systemic safety of Intranasal application. When administered at standard recommended therapeutic dosage, the Intranasal antihistamines do not cause significant sedation or impairment of psychomotor function, effects that would be evident when these agents are administered orally at a therapeutically relevant dosage. The systemic bioavailability of Intranasal corticosteroids varies from <1% to up to 40-50% and influences the risk of systemic adverse effects. Because the dose delivered topically is small, this is not a major consideration, and extensive studies have not identified significant effects on the hypothalamic-pituitary-adrenal axis with continued treatment. A small effect on growth has been reported in one study in children receiving a standard dosage over 1 year, however. This has not been found in prospective studies with the Intranasal corticosteroids that have low systemic bioavailability and therefore the judicious choice of Intranasal formulation, particularly if there is concurrent corticosteroid inhalation for asthma, is prudent. There is no evidence that such considerations are relevant to shorter-term use, such as in intermittent or seasonal disease. Intranasal therapy, which represents a major mode of drug delivery in allergic rhinitis, thus has a very favourable benefit/risk ratio and is the preferred route of administration for corticosteroids in the treatment of this disease, as well as an important option for antihistaminic therapy, particularly if rapid symptom relief is required.
T F Beattie - One of the best experts on this subject based on the ideXlab platform.
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comparison of morphine concentration time profiles following intravenous and Intranasal diamorphine in children
Archives of Disease in Childhood, 2009Co-Authors: S Kidd, S J Brennan, R. Stephen, Robert A Minns, T F BeattieAbstract:BACKGROUND: Current best practice for treating acute severe pain in children is to administer intravenous or Intranasal opioid. Intranasal diamorphine offers less traumatic analgesia than the potentially difficult and distressing intravenous route. However, there has been no direct comparison of Intranasal and intravenous diamorphine nor are there pharmacokinetic data for Intranasal diamorphine in children. OBJECTIVE: To compare plasma morphine concentration-time profiles following Intranasal and intravenous diamorphine administration. DESIGN: Observational. SETTING: A&E department in a city-centre paediatric teaching hospital. PATIENTS: Children, aged 3-13 years, with isolated limb fracture. INTERVENTIONS: An intravenous catheter was sited and baseline blood taken. The first 12 children received intravenous diamorphine (0.1 mg/kg), and the subsequent 12 Intranasal diamorphine (0.1 mg/kg) in 0.2 ml sterile water drops. Subsequent samples were taken at 2, 5, 10, 20, 30 and 60 min. MEASUREMENTS: Plasma morphine radioimmunoassay. RESULTS: Peak plasma morphine concentrations were higher (median 109 vs 36 nmol/l), and occurred earlier (median 2 vs 10 min), with greater area under the curve (3761 vs 1794 nmol/l/h) following intravenous compared to Intranasal diamorphine (all p<0.001, Mann-Whitney U test). Higher plasma concentrations at 60 min (47 vs 32 nmol/l) were also observed following intravenous diamorphine (p = 0.01, Mann-Whitney U test). CONCLUSIONS: Our evidence supports the wider use of diamorphine administration by nasal drops in children, as it shows that adequate plasma levels of morphine are usually achieved. However, we demonstrated significantly attenuated and delayed peak plasma morphine levels with lower levels at 1 h with Intranasal compared with intravenous diamorphine.
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Comparison of morphine concentration–time profiles following intravenous and Intranasal diamorphine in children
Archives of Disease in Childhood, 2009Co-Authors: S Kidd, S J Brennan, R. Stephen, Robert A Minns, T F BeattieAbstract:Background: Current best practice for treating acute severe pain in children is to administer intravenous or Intranasal opioid. Intranasal diamorphine offers less traumatic analgesia than the potentially difficult and distressing intravenous route. However, there has been no direct comparison of Intranasal and intravenous diamorphine nor are there pharmacokinetic data for Intranasal diamorphine in children. Objective: To compare plasma morphine concentration–time profiles following Intranasal and intravenous diamorphine administration. Design: Observational. Setting: A&E department in a city-centre paediatric teaching hospital. Patients: Children, aged 3–13 years, with isolated limb fracture. Interventions: An intravenous catheter was sited and baseline blood taken. The first 12 children received intravenous diamorphine (0.1 mg/kg), and the subsequent 12 Intranasal diamorphine (0.1 mg/kg) in 0.2 ml sterile water drops. Subsequent samples were taken at 2, 5, 10, 20, 30 and 60 min. Measurements: Plasma morphine radioimmunoassay. Results: Peak plasma morphine concentrations were higher (median 109 vs 36 nmol/l), and occurred earlier (median 2 vs 10 min), with greater area under the curve (3761 vs 1794 nmol/l/h) following intravenous compared to Intranasal diamorphine (all p Conclusions: Our evidence supports the wider use of diamorphine administration by nasal drops in children, as it shows that adequate plasma levels of morphine are usually achieved. However, we demonstrated significantly attenuated and delayed peak plasma morphine levels with lower levels at 1 h with Intranasal compared with intravenous diamorphine.
A Siibergeld - One of the best experts on this subject based on the ideXlab platform.
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Intranasal administration of the ghrp hexarelin accelerates growth in short children
Clinical Endocrinology, 1995Co-Authors: Zvi Laron, Jenny Frenkel, R Deghenghl, S Anin, B Klinger, A SiibergeldAbstract:Summary OBJECTIVE Hexarelin is a recently synthesized small growth hormone releasing peptide (GHRP) (His-D-methyl-Trp-Ala-Trp-D-Phe-Lys-NH2). It Is actlve by intra-venous, oral and Intranasal administration In animals and man. The aim of this study was to find out whether longterm administration of this peptlde would promote growth In short chlldren. DESIGN AND PATIENTS Intranasal hexareiin was administered in a dose of 60 pglkg thrice dally to 8 prepubertal short children aged 4-11-6 years for perlods of up to months. RESULTS Hexarelln treatment stimulated Insulin-like growth factor-i (IGF-I) secretion ralsing the level from 10.4 ± 3.9 (SD) to 141 f 46 nmoill (P < 0.004). The rise IGF-l led to a significant Increase In the mean (±SD) linear growth velocity from 53 ± 08 to 8 3 ± 1.7 cm/year (P < 0.0001). There was also a slgniflcant decrease skinfold thickness despite Increase in body weight and an Increase in head circumference. Additional flndlngs were a rlse in serum phosphate from 1–5 ± 01 to 1–8 ± 01 mmoi/l (P < 0004) and of aikallne phosphatase from 219 ± 74 to 261 ± 75 U/l (P < 005). CONCLUSIONS The long-term GHIIGF-I stimulating, anabolic and growth promoting effects achieved by intranasai administration of this hexapeptide, seemingly without undeslrable slde-effects, suggests clinical potential for this new class of drugs.
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Intranasal administration of the ghrp hexarelin accelerates growth in short children
Clinical Endocrinology, 1995Co-Authors: Zvi Laron, Jenny Frenkel, R Deghenghl, S Anin, B Klinger, A SiibergeldAbstract:Summary OBJECTIVE Hexarelin is a recently synthesized small growth hormone releasing peptide (GHRP) (His-D-methyl-Trp-Ala-Trp-D-Phe-Lys-NH2). It Is actlve by intra-venous, oral and Intranasal administration In animals and man. The aim of this study was to find out whether longterm administration of this peptlde would promote growth In short chlldren. DESIGN AND PATIENTS Intranasal hexareiin was administered in a dose of 60 pglkg thrice dally to 8 prepubertal short children aged 4-11-6 years for perlods of up to months. RESULTS Hexarelln treatment stimulated Insulin-like growth factor-i (IGF-I) secretion ralsing the level from 10.4 ± 3.9 (SD) to 141 f 46 nmoill (P < 0.004). The rise IGF-l led to a significant Increase In the mean (±SD) linear growth velocity from 53 ± 08 to 8 3 ± 1.7 cm/year (P < 0.0001). There was also a slgniflcant decrease skinfold thickness despite Increase in body weight and an Increase in head circumference. Additional flndlngs were a rlse in serum phosphate from 1–5 ± 01 to 1–8 ± 01 mmoi/l (P < 0004) and of aikallne phosphatase from 219 ± 74 to 261 ± 75 U/l (P < 005). CONCLUSIONS The long-term GHIIGF-I stimulating, anabolic and growth promoting effects achieved by intranasai administration of this hexapeptide, seemingly without undeslrable slde-effects, suggests clinical potential for this new class of drugs.
