Route of administration inhalation

Routes of administration Inhalation, direct contact with skin or eyes Oral and/or parenteral most likely... 

Drug Albuterol Primary Receptor Beta-2 Route of Administration Inhalation Oral Onset of Action (min) 5-15 15-30 Time to Peak Effect 1- 1.5 2- 3 Duration of Action (hr) 3-6 8 or more... 

Some of the early entrants into this field have expanded their activities into delivery routes other than their original core technology, so that they can offer solutions in the transdermal, inhalation and other fields as well as oral formulations. This is hue of Alza, Elan and 3M, the latter being something of a hybrid since it is also a pharmaceutical company in the conventional sense. By contrast, some companies in this field are linked to specific routes of administration Inhale Therapeutic systems, as its name implies, focuses on inhalation technology, while Pharmatec International, one of the oldest-established advanced drag delivery concerns, remains committed to the oral route. 

Animal studies can include the following routes of administration inhalation, dermal, oral gavage, feeding, and intraperitoneal, intravenous, and subcutaneous. Studies can include looking at developmental and reproductive toxicity, neurotoxicity, histopathol-ogy, and carcinogenic end points. 

Toxicity of diazinon to laboratory animals via dermal, inhalation, dietary, and chronic oral routes of administration... 

Table 16.5 Toxicity of Diazinon to Laboratory Animals via Dermal, Inhalation, Dietary, and Chronic Oral Routes of Administration...

Other routes of administration sometimes used in monkey safety assessment studies are intravaginal dosing, topical application, inhalation, and nasal administration. 

No information is available regarding the effects of acute-duration exposure to chlordecone in humans following inhalation, oral, or dermal exposure. Some information is available regarding the effects of acute-duration exposure to chlordecone in animals by the oral route of administration (Cannon and Kimbrough 1979 Chernoff and Rogers 1976 Davis and Mehendale 1980 Desaiah... 

Chronic-Duration Exposure and Cancer. No information is available regarding the toxicity of chronic-duration exposure of humans to mirex by the inhalation or dermal route of administration. Animal studies have not been located for chronic mirex administration by the inhalation or dermal routes however, oral studies exist (Chu et al. 1981a Gaines and Kimbrough 1970 NTP 1990 ... 

Flunisolide is a fast-acting corticoid designed for the treatment of allergic rhinitis, asthma, and other allied respiratory disorders in humans. As the quantum of drug delivered by inhalation (/. e., the usual route of administration of the drug), is invariably small, the plasma-levels attained can also be fairly small. Hence, there is a dire need for a sensitive method of plasma concentration evaluation which is satisfied by radioimmunoassay. 

The route of administration of an NCE is typically the intended clinical route of administration. However, an alternative route may be used if this leads to an increase in systemic exposure of parent drug or major metabolites or if this alternative route satisfies another important objective of the study. For example, it is common to increase the exposure following inhalation administration by associating a subcutaneous administration of the NCE. 

Validation of the Model. The Corley model was validated using chloroform data sets from oral (Brown et al. 1974a) and intraperitoneal (Ilett et al. 1973) routes of administration and from human pharmacokinetic studies (Fry et al. 1972). Metabolic rate constants obtained from the gas-uptake experiments were validated by modeling the disposition of radiolabeled chloroform in mice and rats following inhalation of chloroform at much lower doses. For the oral data set, the model accurately predicted the total amounts of chloroform metabolized for both rats and mice. 

Interroute Extrapolation. The Corley model used three routes of administration, intraperitoneal, oral and inhalation, in rats and mice to describe the disposition of chloroform. This data was validated for humans by comparing the model output using the animal data with actual human data from human oral chloroform pharmacokinetic studies. Using the human pharmacokinetic constants from the in vitro studies conducted by Corley, the model made adequate predictions of the amount of chloroform metabolized and exhaled in both males and females. 

Interroute Extrapolation. Inhalation and oral routes of administration were examined in the Reitz model however, interroute extrapolations were not specifrcally addressed in the Reitz model. 

Phil Kysor and I similarly developed a TRI to represent a subject s response to BZ. We combined changes in blood pressure (BP), heart rate (HR) and performance on Number Facility (NF), using a scale from 1- 9 for each variable. It helped us to compare responses to BZ given by various routes of administration. Eventually we could combine intravenous, intramuscular, oral, inhalation and percutaneous responses using the TRI as an indicator of relative effectiveness. Fig. 4 shows idealized response curves for various intensities of BZ response. 

In 1960-1961, not only various routes of administration were examined but many different performanee measures, pilot studies of assay teehniques, effeetiveness of treatment with THA, group interaetion, military task performanee and eomparison of response to a seeond dose (as well as eomparison of inhalation to oral route and effeetiveness of partiele size) were studied. However, the number of subjeets used in eaeh study and eompleteness of doeumentation were both insuffieient to permit meaningful statistieal eomparisons. 

LSD, relatively little systematic testing of performance over a range of LSD dosage and throughout the duration of its action had been reported. We therefore undertook studies that would reveal the dose-response relationship with more precision, initially by the oral route and later by intravenous or inhalation routes of administration. A total of approximately 100 subjects were tested between 1961 and 1966, at... 

With regard to the systemic administration of smaller proteins (<20 kDa), the development of insulin for inhalation has shown that the pulmonary route is a feasible route of administration. However, advanced inhalation devices and formulations were required to obtain a reproducible lung deposition. It will be especially necessary to deal with the problems that occur when drugs with a small therapeutic window are administered. To enable widespread use of the lung as port of entry for these small proteins, future developments should be directed towards more simple inhalation devices which still give a high and reproducible lung deposition. The formulations that will be required for these proteins are likely to be much more complex and advanced than those that are currently used. Examples are formu-... 

Distribution, including accumulation of an absorbed substance, will be the same irrespective of the route of administration. However, distribution and accumulation at the site of apphcation (inhalation, oral, dermal) may depend on the route of administration. In such cases, local accumulation may occur and may be responsible for tissue damage. In these cases, systemic toxicokinetics of the substance may be of limited relevance for the risk assessment. It is generally not cmcial for risk assessment to determine the precise tissue distribution profile for a substance. In certain special cases, however, specific tissue distribution studies may assist or even be essential for the interpretation of available toxicological data. For example, it may be of interest to know whether the substance will cross the blood-brain barrier, the placenta barrier, or will accumulate in specific tissues. 

TG 402 and 403 are similar to the deleted TG 401, except for the route of administration, and are therefore expected to be deleted when new test guidelines for the dermal and inhalation routes become adopted. 

A tolerable intake may have different units depending on the route of administration upon which it is based, and is generally expressed on a daily or weekly basis. For the oral and dermal routes, a tolerable intake is generally expressed on a body weight basis, e.g., mg/kg body weight per day. Though not strictly an intake, tolerable intakes for inhalation are generally expressed as an airborne concentration, e.g., mg/m. ... 

The transformation of a drug into a medicinal product is a complex process that is controlled by a range of competing factors. The formulator must amalgamate the preformulation information and the clinical indication, which may suggest a particular route of administration (e.g. inhalation of salbutamol. Table 2.2), with toxicology and biopharmaceutical data determining... 

Ideally, toxicology studies should mimic, as near as possible, human exposure. Thus, both the route of administration and the exposure should, where possible, be similar to that in man. The classic route of administration in man is oral and thus most toxicology studies are conducted by the oral route. Elowever, parenteral routes may be used either to mimic the clinical route or to ensure exposure. The administration of some medicines is directly on to highly differentiated surfaces such as the alveolar surface of the lungs or the skin. It is, therefore, important to assess the topical irritancy, absorption and subsequent systemic toxicity following such applications. It should be remembered that some compounds, for example, chlorinated hydrocarbons, may be more toxic when given by the inhalation route than when given orally or may directly affect... 

Costs are approximate (as of 2(X)2) and assume oral (gavage) administration and include costs of assay to confirm dose concentration and bioassay of pharmacokinetic samples. Significant variations for the same study design will be found between different contractors ( 20%), different study designs ( 25%) and different routes of administration (intravenous 25%, inhalation by snout only + 50-100%). 

Drugs metabolized by COMT Administer drugs known to be metabolized by COMT (ie, isoproterenol, epinephrine, norepinephrine, dopamine, dobutamine, methyidopa, apomorphine, isoetherine, bitolterol) with caution in patients receiving entacapone regardless of the route of administration (including inhalation), as their interaction may result in increased heart rates, arrhythmias, and excessive changes in blood pressure. 

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