Oral improved

Mastocytosis (oral) Improves diarrhea, flushing, headaches, vomiting, urticaria, abdominal pain, nausea and itching in some patients. 

Deriva.tives, The most important derivatives of 1,2,3,4-benzenetetrol are the ubiquiaones, eg, coenzyme Q, which are dimethoxytoluquiaones with polyisoprenoid side chains (61). They occur ia plants and animals. Mice with hereditary muscular dystrophy have a deficiency of coenzyme Q ia their heart and hind leg muscles. Therapeutic adrninistration of coenzyme Q /7339-63-5] produces physical improvement and a significantly prolonged lifespan (212). Coenzyme Q also has been used to treat deafness when adrninistered either orally or parenteraHy (213). 

Improvements in asthma treatment include the development of more effective, safer formulations of known dmgs. The aerosol adrninistration of P2-agonists or corticosteroids results in a decrease in side effects. Also, the use of reUable sustained release formulations has revolutionized the use of oral xanthines which have a very narrow therapeutic index (see Controlled release technology). For many individuals, asthma symptoms tend to worsen at night and the inhaled bronchodilatots do not usually last through an entire night s sleep (26,27). 

Ephedrine, which is not a catecholamine, has weak oral activity as a bronchodilator and although it has some direct action at adrenergic receptors, its predominant mode of action is by displacing norepinephrine from storage vesicules. 2"Agonists which are in use or are under investigation are the result of quests for improved selectivity, retention of potency, oral activity, and longer duration of action. 

The first SRS-A antagonist, FPL-55712 (26) (149), was discovered before the stmctures of the leukotrienes were detemiined. Although this compound is relatively weak as an antagonist and suffers from a very short half-life in vivo, it played an important role both in leukotriene stmcture elucidation and as a model for later antagonists. In work stmcturaHy related to FPL-55712, LY-171883 was developed (27) (150). LY-171883 was evaluated in several clinical trials before development was stopped. Orally adrninistered, LY-171883 blocked slightly the response to aerosol LTD improved pulmonary function (FEV ) in mild asthmatics (151), decreased the sensitivity of asthmatics to cold air-induced bronchoconstriction (152), and significantly reduced the bronchoconstrictor response to inhaled antigen (153). However, in all these studies the beneficial effects were minimal. 

The development of new antibiotics to combat resistance, and to provide easier oral administration and improved pharmacokinetics has been successful through synthetic modifications. This approach has been particularly rewarding in the area of P-lactams. The commercial importance of the P-lactams is evident from Table 3 which gives the market share of antibacterials. Fully 62% of the 1989 world antibacterial market belonged to the cephalosporin and penicillin P-lactams (20). 

The pharmacology of penicillins differs markedly from compound to compound but has been well reviewed (57). The majority of derivatives, including penicillin G and the antipseudomonal penicillins, ate unstable in gastric acid and ate not available orally. The isoxazolyl penicillins ate relatively acid stable but not consistendy well absorbed by the oral route. Nafcillin and oxacillin ate poody absorbed orally cloxacillin, dicloxacillin, and ducloxacillin ate more teUable. Penicillin V, ampicillin, and patticulady amoxicillin ate relatively well absorbed orally. Esters of ampicillin such as bacampicillin, pivampicillin, and talampicillin improve the level of oral absorption of ampicillin to that achieved by amoxicillin. Absorption can be diminished by food after oral adruinistration, however, and peak blood levels, usually achieved after 1 to 2 h, ate somewhat delayed after ingestion of food. 

Qindamycin, 7(5)-7-chloro-7-deoxyliQcomycin [18323-44-9] (1, R = H, R = Q), also known as Cleocin, first resulted from the reaction of lincomycin and thionyl chloride (54) improved synthetic methods involve the reaction of lincomycin and triphenylphosphine dichloride or triphenylphosphine in carbon tetrachloride (55). Clindamycin is significantly more active than lincomycin against gram-positive bacteria in vitro, and is absorbed rapidly following oral adnainistration. Clindamycin 2-palmitate [36688-78-5], (6, R = R = OC(CH2) 4CH2), 2-palmitate ester of clindamycin, is... 

Ester derivatives of oleandomycia (17, R = CH ) were also pursued leading to commercial development of (31) also known as troleandomycin (TOA), which improved oral bioavadabihty and taste as compared to the parent (135). 

Safety is assessed by subjecting the antioxidant to a series of animal toxicity tests, eg, oral, inhalation, eye, and skin tests. Mutagenicity tests are also carried out to determine possible or potential carcinogenicity. Stabilizers are being granulated and Hquid products are receiving greater acceptance to minimize the inhalation of dust and to improve flow characteristics. 

Areas of Continued Research. Research continues in many academic and pharmaceutical laboratories throughout the wodd with the objective of improving oral contraceptives and better understanding their pharmacological and clinical actions. 

Permeation enhancers are used to improve absorption through the gastric mucosa. Eor example, oral dehvery of insulin (mol wt = 6000) has been reported from a water-in-oH- emulsion containing lecithin, nonesterified fatty acids, cholesterol [57-88-5], and the protease inhibitor aprotinin [9087-70-1] (23). 

An oral dental riase geaeraHy coasists of water, alcohol, a humectant, an emulsifier, flavor, color, and an active agent. Water is the primary vehicle. The alcohol provides bite and is also a formulation aid. The humectant improves the feel ia the mouth and also prevents locking of the cap to the container between uses glycerin or noncrystaUiziag sorbitol may be satisfactory. The emulsifier is a nonionic type, for example, a polyoxyethylene—polyoxypropylene block copolymer or a polyoxyethylene sorbitan fatty acid ester. Flavors are generally a type of mint or cinnamon. Colors are FD C or D C. 

In Older to improve the poor oral absorption of carbenicillin [4697-36-3] a bpophilic rndanyl ester has been formulated, Geocillin [33331-88-3] (5). Prednisolone [30-24-8] a steroid, is derivatized to its C-21 hemisuccinate sodium salt (6) to make it extremely water-soluble (108). 

Various materials are used in dental prosthetic practice for the preparation of dental implants, crowns, and bridges. Some of these materials contain copper, which is added in order to improve mechanical or/and chemical properties, but some of them may contain the copper as an impurity. Considering the fact that dental implants remain in the oral cavity for a long time, and that they are exposed to the corrosive action of oral fluids and various kinds of food and beverages, it is necessary to check their possible harmful effects upon the human health. 

Norfloxacin (1, R = C2H5, R = H), a typical example, exhibits broad-spectrum activity and is useful in the treatment of upper respiratory tract and urinary infections [7] Lomefloxacin (2), a very recent introduction, is a third-generation product that, given once daily, is especially useful against pathogens resistant to cephalosponns, penicillins, and aminoglycosides [4] Floxacillin (J) is a stable, orally active antibacterial with improved activity over thenonfluonnated product (cloxacillin) [5]... 

One of the most popular orally active penicillins in present clinical use is amoxicillin (12). Its oral effectiveness and broad spectrum of activity against common pathogens as well as its better absorption than its closest precedent competitor, ampicillin (14), largely accounts for this. Higher blood and tissue levels of antibiotics is another means of dealing with resistance. In an attempt to achieve yet further improvements in oral bioavailability and hence blood and ti.ssue levels of amoxicillin, the prodmg fumoxicillin (13) is prepared from amoxicillin (12) by treatment with furfural [3]. The imine moiety is less basic than the primary amine so that the isoelectric point of fumoxicillin is more on the acid side than is that of amoxicillin. 

Most ACE inhibitors are prodrugs, with the exceptions of captopril, lisinopril, and ceranapril. Prodrugs exert improved oral bioavailability, but need to be converted to active compounds in the liver, kidney, and/or intestinal tract. In effect, converting enzyme inhibitors have quite different kinetic profiles with regard to half time, onset and duration of action, or tissue penetration. 

Biguanide Metformin Improve insulin action Oral... 

Thiazolidinediones Pioglitazone, rosiglitazone Improve insulin action (PPARy agonists) Oral... 

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