Oral contrast

Oral administration of the H3 receptor agonist BP 2.94 (20-30 mg/kg) to rats produced a dose-dependent increase in NREM sleep without a significant change in wakefulness or REM sleep. With the highest dose of BP 2.94 (30 mg/kg), the increase in NREM sleep was observed during the second hour and the effect lasted for 6 h. Pretreatment with the H3 receptor antagonist carboperamide (30 mg/kg) prevented the sleep-inducing effects of BP 2.94. In contrast, oral administration of carboperamide (20-30 mg/kg) produced a dose-dependent increase in wakefulness with a concomitant decrease in NREM and REM sleep (Monti et al., 1996). 

Iron supplementation is necessary to replete iron stores (Fig. 76-5). Parenteral iron therapy improves response to erythropoietic therapy and reduces the dose required to achieve and maintain target indices. In contrast, oral therapy is often inadequate. 

To supplement depot medication, oral preparations can be used when early warning signals of an impending relapse occur because the pharmacokinetics of depot preparations require months to reach steady-state (see also Pharmacokinetics/Plasma Levels later in this chapter). By contrast, oral administration brings about an altered steady state in several days. We recommend treating most patients with the minimally effective dose to avoid more serious adverse effects, even at the cost of a few more relapses, provided this strategy does not lead to rehospitalization or produce serious impairment in functioning. 

In contrast, oral administration of a willow bark extract showed a low bioavailability of salicin (98). After ingestion of commercial sugar-coated tablets containing willow bark extract corresponding to a total amount of 54.9mg (0.192mmol) salicin, the serum of 12 volunteers showed a peak concentration of only 0.13 pg/mL salicylic acid this is only 5% of the serum... 

In adnlts with chlamydial ocnlar infections such as inclusion conjnnctivitis or trachoma, treatment with oral doxycycline or tetracycline is a recommended strategy (seeTable 11-1). In commnnity-based programs to control trachoma, topical tetracycline ointment administered twice daily on an intermittent schedule (5 consecutive days each month for 6 months) can be useful. However, incomplete cnre and snbseqnent disease transmission can resnlt. In contrast, oral treatment with tetracycline or doxycycline cnres trachoma. 

Reduced survival time in "Ah-responsive" mice (those capable of producing increased levels of cytochrome P-450 enzymes) was observed following a single intraperitoneal dose of 500 mg/kg benzo[a]pyrene (Robinson et al. 1975). In contrast, oral exposure to 120 mg/kg/day benzo[a]pyrene results in reduced survival of "Ah-nonresponsive" mice (those whose P-450 enzymes are not induced by PAHs). 

In vivo assays in mice showed that oral doses of manganese sulfate or potassium permanganate caused micronuclei and chromosomal aberrations in bone marrow (Joardar and Sharma 1990). In contrast, oral doses of manganese chloride did not cause chromosomal aberrations in the bone marrow or spermatogonia of rats (Dikshith and Chandra 1978). A list of in vivo study results is given in Table 2-11. 

Although the average oral availability of furosemide is approximately 60%, oral availability of furosemide varies from 10 to 100%. In contrast, oral availabilities of bumetanide and torsemide are reliably high. Heart failure patients have fewer hospitalizations and better quality of life with torsemide than with furosemide, perhaps because of the more reliable absorption of torsemide. 

Resorption of zinc in the digestive tract occurs mainly in the duodenum, but also in other parts of the small intestine. Resorption efficiency is normally about 30% and is regulated by intracellular ligands. In the transport of zinc into the intestinal cells (similarly to the iron transport) divalent cations are involved. In enterocytes, zinc is bound in metallothionein (at high doses of zinc in the diet) or in a complex with cysteine-rich intestinal protein (CRIP) (at lower doses of zinc). Resorption of zinc is higher in individuals with lower body weight and in cases of lower body saturation by zinc. In contrast, oral administration of high doses of zinc decreases the absorption efficiency. 

Many monocyclic aromatic compounds, including chlorobenzene, dichlorobenzene, trichlorobenzene, tetrachlorobenzene, pentachlorobenzene, ethyl benzene, toluene, and nitrobenzene are not carcinogenic. By contrast, oral administration of hexachlorobenzene to hamsters produced liver tumors, liver haemangiotheliomas, and thyroid adenomas (LARC, 1979). Although hexachlorobenzene is also fetotoxic and produces some teratogenic effects,it is not mutagenic to yeast. Other compounds that are either promoters or known/suspected carcinogens include benzene, 2,6-dinitrotoluene, 2,4,6-... 

Contraceptives, oral Contract maintenance Contrast agents... 

The two synthetic steroidal estrogens which have attained the greatest degree of therapeutic use are ethinyl estradiol [57-63-6] (EE) (5) and its 3-methyl ether, mestranol [72-33-3]((5). In contrast to the naturally occurring estrone derivatives, these acetylenic analogues are orally active and are the main estrogenic components of combination oral contraceptives (see Contraceptives) and certain estrogen replacement products. 

The acute toxicity of MSG is low (31) the oral LD q for humans, calculated on the basis of doses a dministered in different ways to various animals, would represent a single dose greater than 1 kg for a person weighing 70 kg. In contrast, the oral LD q for sodium chloride in rats is 3.75 g/kg body weight (32). 

Extravasation of barium sulfate iato the peritoneal cavity through a perforated GI tract can produce serious adverse reactions. When a perforation is suspected, the use of a water-soluble iodinated contrast medium is iadicated. In this case, oral or rectal administration of sodium or meglumine-sodium salts of diatrizoic acid (6) and oral use ofiohexol (11) are the preferred procedures. 

Sucralfate [54182-58-0] an aluminum salt of sucrose octasulfate, is used as an antacid and antiulcer medication (59). Bis- and tris-platinum complexes of sucrose show promise as antitumor agents (60). Sucrose monoesters are used in some pharmaceutical preparations (21). A sucrose polyester is under evaluation as a contrast agent for magnetic resonance imaging (mri) (61). Oral adrninistration of this substance opacifies the gastrointestinal tract and eliminates the need for purging prior to mri. 

Animal and Human Toxicity. The acute toxicity of lindane depends on the age, sex, and animal species, and on the route of adrninistration. The oral LD q in mice, rats, and guinea pigs is 86, 125—230, and 100—127 mg/kg, respectively. In contrast, most of the other isomers were considerably more toxic (94,95). Some of the other toxic responses caused by lindane in laboratory animals include hepato- and nephotoxicity, reproductive and embryotoxicity, mutagenicity in some short-term in vitro bioassays, and carcinogenicity (80). The mechanism of the lindane-induced response is not known. Only minimal data are available on the mammalian toxicides of hexachlorocyclopentadiene. 

Transdermal dmg dehvery is associated with a relatively long time lag before the onset of efficacy, and removal of the system is foUowed by a correspondingly extended fall in plasma concentration, which probably results from formation of a dmg depot in the skin that dissipates slowly. The time lag is approximately 3 to 5 h for many dmgs that have low binding in the skin (49—51), but may be considerably longer. In contrast, plasma dmg levels may be obtained between 2 and 5 min by the oral, buccal, or nasal routes. 

The discovery of the utility of the bis-chromone carboxylic acid derivative cromolyn sodium in the treatment of asthma and related allergies has led to an intensive, and thus far not very fruitful, effort to discover analogues which would show oral activity in contrast to the lead which must be administered by inhalation. Preparation of a typical analogue, proxicromil (63), starts with the O-allylated phenol 57. Claisen rearrangement leads to the corresponding C-allylated product 58. 

FIGURE 8.25 Repeated oral administration of drags leads to steady-state plasma concentrations. If elimination is rapid and administration not often enough, then an elevated and therapeutically effective steady-state concentration may not be achieved (green lines). In contrast, if elimination is very slow (or administration too often), then an accumulation of the drag may be observed with no constant steady state (red line). Bine line shows a correct balance between frequency of administration and elimination. 

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