Intranasal route

Takafuji, S., et al., Diesel-exhaust particulates inoculated by the intranasal route have an adjuvant activity for IgE production in mice, J. Allergy Clin. Immunol., 79, 639, 1987. 

Nasal Administration. A route that has gained increasing popularity of late for pharmaceutical administration in humans is the intranasal route. The reasons for this popularity are the ease of use (and, therefore, ready patient acceptance and high compliance rate), the high degree and rate of absorption of many substances (reportedly for most substances up to 1000 molecular weight McMartin et al., 1987), and the avoidance of the highly acid environment in the stomach and first-pass metabolism in the liver (particularly important for some of the newer peptide moieties) (Attman and Dittmer, 1971). The only special safety concerns are the potential for irritation of the mucous membrane and the rapid distribution of administered materials to the CNS. 

Mecfianism of Action An ergotamine derivative, alpha-adrenergic blocker that directly stimulates vascular smooth muscle. May also have antagonist effects on sero-fonin. Therapeutic Effect Peripheral and cerebral vasoconstriction. Pharmacokinetics Slow, incomplete absorption from the gastrointestinal (GI) tract rate of absorption of intranasal route varies. Protein binding greaterthan 90%. Undergoes extensive first-pass metabolism in liver. Metabolized to active metabolite. Eliminated in feces via biliary system. Half-life 7-9 hr. 

A small number of biopharmaceuticals are delivered by nonparenteral means. Recombinant DNase is given by inhalation aerosol to reduce the viscosity of mucus in the lungs of patients with cystic hbrosis. A platelet-derived growth factor in the form of a gel is administered topically for wound healing. Several hormones and peptides are administered in solution by the intranasal route. A solution of an antisense drug used for the treatment of cytomegalovirus retinitis is injected directly into the eye. 

Additional considerations for inhalation/intranasal route acute inhalation, application site, and pulmonary sensitization studies for parenteral route acute parenteral toxicity and application site studies mucosal use application site evaluation transdeimal and topical drugs application site and phototoxicity/photoallergy evaluation. Photocarci-nogenicity is a conditional option for transdeimal and topical excipients. 

Perez-Reyes et al.8 estimated that only 32% of a dose of cocaine base placed in a pipe is actually inhaled by the smoker. Cone9 compared the pharmacokinetics and pharmacodynamics of cocaine by the intravenous, intranasal, and smoked routes of administration in the same subjects. Venous plasma cocaine concentrations peaked within 5 min by the intravenous and smoked routes. Estimated peak cocaine concentrations ranged from 98 to 349 ng/ml and 154 to 345 ng/ml after intravenous administration of 25-mg cocaine hydrochloride and 42-mg cocaine base by the smoked route, respectively. After dosing by the intranasal route (32 mg cocaine hydrochloride) estimated peak plasma cocaine concentrations ranged from 40 to 88 ng/ml after 0.39 to 0.85 h.9 In this study, the average bioavailability of cocaine was 70.1% by the smoked route and 93.7% by the intranasal route. Jenkins et al.10 described the correlation between pharmacological effects and plasma cocaine concentrations in seven volunteers after they had smoked 10 to 40 mg cocaine. The mean plasma... 

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. 

Pulsed (i.e. intermittent) estrogen treatment, given by the intranasal route, has been examined as a means of reducing the risk or rate of postmenopausal bone loss and hence osteoporosis. In a 2-year randomized, placebo-con-trolled study, in 386 women, hysterectomized patients received 17-beta-estradiol, 150 or 300 micrograms/day for 2 years, and women with an intact uterus received... 

The above-mentioned results concerning Par j 1 biodistribution were obtained in normal volunteers [44, 45], In other experiments [48, 49] radio-labelled Par j 1 was administered to volunteers allergic to P judaica by the sublingual or intranasal route. For the sublingual route the preparation was administered in tablets, as in a normal course of immunotherapy the tablets were kept in the mouth until dissolved, then they were swallowed. 

The intranasal route of administration is best for those drugs that either undergo extensive degradation or are poorly absorbed after oral administration. 

Vasopressin is administered by intravenous, intramuscular, or intranasal routes oral absorption is slight. The half-life of circulating ADH is approximately 20 minutes, with renal and hepatic catabolism via reduction of the disulfide bond and peptide cleavage. A small amount of vasopressin is excreted as such in the urine. 

The low oral bioavailability of hormone-replacement drugs due to intestinal and first-pass metabolism requires the use of higher doses of these drugs, which are associated with many side effects. Parenteral administration of sex steroids as well as use of the transdermal route has been viewed as an alternative. However, the transdermal route has certain limitations, such as the visibility and palpability of the patch as well as possible skin irritation. These drawbacks have limited the use of this route. The intranasal route has therefore been considered as an alternative [128],... 

Gopinath, P. G., Gopinath, G., and Kumar, T. C. A. (1978), Target site of intranasally sprayed substances and their transport across the nasal mucosa. A new insight into the intranasal route of drug delivery, Curr. Ther. Res., 23, 596-607. 

The intranasal route of administration is also not without problems when abused. Some non-fatal complications... 

Virosomes are liposomes containing viral fusion proteins that allow efficient entering into cells fusion with endosome membranes. Viral fusion proteins become activated in the low pH environment in the endosome to release its contents into the cytosol. Hepatitis A and influenza vaccines constructed on virosomes elicited fewer local adverse reactions than did their classic counterparts and displayed enhanced immunogenicity. Virosome-formulated influenza vaccine has also been shown to be safe and immunogenic when administered by the intranasal route. Other studies have suggested that immunopotentiating reconstituted influenza virosomes can be a suitable delivery system for synthetic... 

In a randomized, double-blind, placebo-controlled comparison of intranasal and intramuscular atropine in 80 children, the intranasal route was equally effective at preventing halothane-induced bradycardia (59). 

---