Intranasal administration

Oxytocin is contraindicated in patients with known hypersensitivity to the drug, cephalopelvic disproportion, unfavorable fetal position or presentation, in obstetric emergencies, situations of fetal distress when delivery is not imminent, severe toxemia (preeclampsia, eclampsia), hypertonic uterus, during pregnancy (intranasal administration), when there is total placenta previa, or to induce labor when vaginal delivery is contraindicated. Oxytocin is not expected to be a risk to the fetus when administered as indicated. When oxytocin is administered with vasopressors, severe hypertension may occur. 

Further SAR studies on the cyclopentane scaffold have included variation of the hydrophobic side-chain to incorporate a carboxamide substituent (Chand et al. 2004), equivalent to the C6-carboxamide derivatives of zanamivir, and extension of the length of the hydrophobic side-chains (Chand et al. 2005a). Analogues that incorporate a longer 4-heptyl side-chain showed comparable efficacy to 34 upon oral and intranasal administration in mice, and comparable or better efficacy than oseltamivir and zanamivir (Chand et al. 2005a). 

Besides the inhalative use, the development of a drug formulation for A9-THC has to address other bioavailabihty questions. A major problem is the hpophiUcity and poor solubiUty in water, hmiting oral uptake when given orally. Because of this, other parenteral routes of apphcation are imder investigation like puhnonal uptake by vaporization, subUngual or intranasal administration, and apphcation by injection of A9-THC incorporated in hpo-somes. 

Primary therapy is based on disease severity and type of hemorrhage.7 Most patients with mild to moderate disease and a minor bleeding episode can be treated with l-desamino-8-D-arginine vasopressin [desmopressin acetate (DDAVP)], a synthetic analog of the antidiuretic hormone vasopressin. DDAVP causes release of von Willebrand factor (vWF) and factor VIII from endogenous storage sites. This formulation increases plasma factor VIII levels by three- to fivefold within 30 minutes. The recommended dose is 0.3 mcg/kg intravenously (in 50 mL normal saline infused over 15 to 30 minutes) or subcutaneously or 300 meg intranasally via concentrated nasal spray every 12 hours. Peak effect with intranasal administration occurs 60 to 90 minutes after administration, which is somewhat later than with intravenous administration. Desmopressin infusion may be administered daily for up to 2 to 3 days. Tachyphylaxis, an attenuated response with repeated administration, may occur after several doses.8... 

A. S. Harris, Biopharmaceutical aspects of the intranasal administration of peptides, in Delivery Systems for Peptides (S. S. Davis, L. Ilium, and E. Tomlinson, eds.), Plenum Press, New York, 1986, p. 191. 

Vollrath, L., Semm, P. Gammel, G. (1981). Sleep induction by intranasal administration of melatonin. Adv. Biosci. 29, 327-9. 

Subcutaneous injection/ intranasal administration 26 d Allergic responses [109]... 

Gutierro I, Hernandez RM, Igartua M et al (2002) Size dependent immune response after subcutaneous, oral and intranasal administration of BSA loaded nanospheres. Vaccine 21 67-77... 

LAIV is made with live, attenuated viruses and is approved for intranasal administration in healthy people between 5 and 49 years of age (Table 41-2). Advantages of LAIV include its ease of administration, intranasal rather than intramuscular administration, and the potential induction of broad mucosal and systemic immune response. 

Side effects of triptans include paresthesias, fatigue, dizziness, flushing, warm sensations, and somnolence. Minor injection site reactions are reported with SC use, and taste perversion and nasal discomfort may occur with intranasal administration. Up to 15% of patients report chest tightness, pressure, heaviness, or pain in the chest, neck, or throat. Although the mechanism of these symptoms is unknown, a cardiac source is unlikely in most patients. Isolated cases of myocardial infarction and coronary vasospasm with ischemia have been reported. 

It seemed that the reaction appeared to set in more rapidly and was over more quickly with intranasal administration than orally administered LSD-25, thus approximating an intravenous injection. 

Peak concentration of B-12 after intranasal administration is 1 to 2 hours Bioavailability is 8.9%. 

Second-generation agents - Intranasal administration of azelastine yields peak levels in 2 to 3 hours, with an elimination half-life of 22 hours. 

Absorption/Distributton - Gl and sublingual absorption of ergotamine is incomplete and erratic following oral administration, peak blood levels are reached in about 2 hours. Following intranasal administration, however, the mean bioavailability of dihydroergotamine mesylate is 32% relative to the injectable administration. 

Pharmacokinetics Some absorption systemically. The duration of action of intranasal administration ranges from 30 minutes to 4 hours. The duration of the mydriatic effect is roughly 3 hours after administration of the 2.5% solution but maybe as long as 7 hours after the 10% solution. 

Receptor-mediated endocytosis may be possible because receptors have a high affinity for BDNF (Deckner et al. 1993). A linear relation between intranasal administration of -labeled NGF and brain concentrations of the compound suggest that this transportation is not mediated by receptors and that this releasing method of agents to the brain via olfactory nerves may be effective for many therapies (Frey et al. 1995). BDNF and the insulin-type growth factor (IGF-1) are currently used in clinical studies (Appel 1997). 

J Pharmacol Exp Ther 184 506-514, 1973 Thompson JW, Weiner RD, Myers CP Use of ECT in the United States in 1975, 1980, and 1986. Am J Psychiatry 151 1657-1661, 1994 Thoren P, Asberg M, Gronholm B, et al CMI treatment of OCD. A controlled clinical trial. Arch Gen Psychiatry 37 1281-85, 1980 Thorne RG, Perfetti PA, Emory CR, et al Quantitative assessment of transneuronal transport to the rat olfactory bulb following intranasal administration of wheat germ agglutinin-horseradish peroxidase. Neurobiol Aging 13 (suppl 1) 132-133, 1992... 

The provocation of mucosal immunity against a given antigen can be achieved by other means besides oral ingestion. For example, intranasal administration of vaccine proteins can improve local mucosal immunity and enable large populations to be immunized at a lower cost. Plant-derived vaccines provide hope for more immunogenic, more effective and... 

After intranasal administration maximum serum concentration are achieved within 10 to 45 minutes. It is 80% bound to plasma proteins. 

Although there is no doubt that amphetamines or other psychomotor stimulants induce an initial euphoria, there is considerable doubt that they can serve as long-lasting antidepressants. Cocaine, for example, produces a euphoria almost immediately after i.v. injection and within a few minutes after intranasal administration, but the euphoria, as well as the tachycardia, decrease at a slightly faster rate than the level of plasma cocaine. A second dose given 1 hour later fails to produce a similar level of euphoria or tachycardia, suggesting a rapid tachyphylaxis. 

Hjortkjaer RK, Bechgaard E, Gizurason S, et al. Single- and repeated-dose local toxicity in the nasal cavity of rabbits after intranasal administration of different glycols for formulations containing benzodiazepines. J Pharm Pharmacol 1999 51(4) 377. 

A two-compartment open linear model has been described for the pharmacokinetic profile of cocaine after intravenous administration.14 The distribution phase after cocaine administration is rapid and the elimination half-life estimated as 31 to 82 min.14 Cone9 fitted data to a two-compartment model with bolus input and first-order elimination for the intravenous and smoked routes. For the intranasal route, data were fitted to a two-compartment model with first-order absorption and first-order elimination. The average elimination half-life (tx 2 3) was 244 min after intravenous administration, 272 min after smoked administration, and 299 min after intranasal administration. 

Javaid, J.I., Musa, M.N., Fischman, M., Schuster, C.R., and Davis, J.M., Kinetics of cocaine in humans after intravenous and intranasal administration, Biopharm. Drug Disp., 4, 9-18, 1983. 

Ben-Yedidia, T., Tarrab-Hazdai, R., Schechtman, D. and Arnon, R. (1999) Intranasal administration of synthetic recombinant peptide-based vaccine protects mice from infection by Schistosoma mansoni. Infection and Immunity 67, 4360-4366. 

Mielcarek, N., Riveau, G., Remoue, F., Antoine, R., Capron, A. and Locht, C. (1998) Homologous and heterologous protection after single intranasal administration of live attenuated recombinant Bordetella pertussis. Nature Biotechnology 16, 454-457. 

Sun, J.B., Mielcarek, N., Lakew, M., Grzych, J.M., Capron, A., Holmgren, J. and Czerkinsky, C. (1999) Intranasal administration of a Schistosoma mansoni glutathione S-transferase-cholera toxoid conjugate vaccine evokes antiparasitic and antipathological immunity in mice. The journal of Immunology 163, 1045-1 052. 

Protirelin is generally given intravenously (as a bolus of 200 micrograms), as absorption after oral and intranasal administration is unpredictable. 

Gizurarson S, Bechgaard E. Intranasal administration of insulin to humans. Diabetes Res Clin Pract 1991 12(2) 71-84. 

Acute water intoxication has produced maternal cerebral edema and convulsions in under 50 reported cases, both with intravenous and intranasal administration (10). The risk is higher in women given high doses of the drug in combination with salt-poor intravenous fluids. In rare cases this has been fatal. 

Hall G, Houghton C, Rahbek J, Lamb J, Jarman E Suppression of allergen reactive Th2 mediated responses and pulmonary eosinophilia by intranasal administration of an immunodominant peptide is linked to IL-10 production. Vaccine 2003 21 549-561. 

Yasue M, Yokola T, Fukada M, Takai T, Suko M, Okudaira H, Okumura Y Hyposensitization to allergic reaction in Der f 2-sensitized mice by intranasal administration of a mutant of rDer f 2, C8/119S. Clin Exp Immunol 1998 113 1-9. 

Astori M, Gamier C, Kettner A, Dufour N, Corradin G, Spertini F Inducing tolerance by intranasal administration of long peptides in naive and primed CBA/J mice. J Immunol 2000 165 3497-3505. 

Relatively recently intranasal administration of the allergen has been adopted. In particular, specific local nasal immunosensitizing therapy (LNIT) that was first used by Herxheimer [1] in 1951 is based on direct immunotoler-ance induction in the shock organ with a reduced risk of side effects and costs. The standard treatment schedule consists of an induction phase with increasing dosages followed by a maintenance phase. Other treatment schedules consist of a constant dosage [7, 8],... 

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