Liver oral administration routes

Autopsy tissues and other biologic specimens from people fatally poisoned with endrin (by the oral or an unspecified route) were analyzed (Tewari and Sharma 1978). The "fatal period" (presumed to be the time from onset of symptoms until death) for the subjects studied ranged from 1 to 6 hours. As is characteristic of oral administration, highest tissue concentrations were observed in the stomach (1.04-14.5 mg/100 g), intestine (1.31-66 mg/100 g), and liver (0.94-20 mg/100 g), followed by kidney, spleen, heart, and lung. Blood concentrations were low (0.43-0.85 mg/100 g) compared to tissue concentrations. 

The Mann et al. (1985) study is limited in that too few animals were used, organs other than the liver were not adequately evaluated, and only males were studied. Although an adequate acute-duration oral study would be useful to corroborate or refute the thyroid effects seen in the Mann et al. (1985) study, this does not represent a data need, since an acute oral MRL has been derived. Ingestion of contaminated drinking water is expected to be the predominant route of exposure for individuals living in the vicinity of hazardous waste sites. However, acute-duration inhalation and dermal studies in animals are needed to assess the potential toxicity of di- -octylphthalate following exposure via these routes because there are insufficient pharmacokinetic data available to support the extrapolation of data obtained after oral administration to other routes of exposure. 

These results are similar to those after oral administration and suggest that 1,2-dibromoethane is rapidly absorbed and distributed but retained to only a limited extent mainly in the kidneys, liver, and stomach, regardless of the route of exposure and the species tested. 

Diphenolmethane derivatives (p. 177) were developed from phenolphthalein, an accidentally discovered laxative, use of which had been noted to result in rare but severe allergic reactions. Bisac-odyl and sodium picosulfate are converted by gut bacteria into the active colon-irritant principle. Given by the enteral route, bisacodyl is subject to hydrolysis of acetyl residues, absorption, conjugation in liver to glucuronic acid (or also to sulfate, p. 38), and biliary secretion into the duodenum. Oral administration is followed after approx. 6 to 8 h by discharge of soft formed stooL When given by suppository, bisacodyl produces its effect within 1 h. 

Pharmacokinetics Colchicine is rapidly absorbed after oral administration peak plasma concentrations occur in 0.5 to 2 hours. High colchicine concentrations are found in the kidney, liver, and spleen. It is metabolized in the liver. Excretion occurs primarily by biliary and renal routes. 

They are given by oral, parenteral and topical route. Oral bioavailabiHty of synthetic cortico-steroids is high. Hydrocortisone after oral administration undergoes extensive first pass metabolism in liver. 

Clarithromycin is readily and rapidly absorbed after oral administration and is metabolized significantly in liver. Active metabolite is excreted by kidney and other routes. 

After oral administration it exhibits inconsistent absorption. Hence it is administered by IV route and is metabolised in liver. 

It is well absorbed by oral or parenteral routes and is excreted relatively slowly. Although tylosin is extensively metabolized, the parent compound always occurs in tissues at higher concentration than its metabolites (94). After oral administration of radiolabeled tylosin to swine, almost all of the radioactivity was excreted through the feces in the form of tylosin A, tylosin D, and dihydrodes-mycosin very low concentrations of these residues were also present in liver and kidney (95). 

The route of administration also determines the level of the residues in the tissues in general, oral dosing of animals results in lower residue concentrations than injections (96, 97). For that reason, detectable residues of parent tylosin cannot be found in swine liver unless the medicated feed contains at least 1000 ppm of the drug (98) residues of the parent compound are also undetectable in poultry tissues following oral administration of tylosin. 

After oral administration, doxycycline is rapidly and well absorbed from the gastrointestinal tract. It has a half-life of 15-22 h, which is longer than that of other tetracyclines. Following administration by various routes, doxycycline is widely distributed in the body, with highest levels in kidney and liver, besides bones and dentine. Doxycycline may be metabolized for up to 40%, and is largely excreted in feces via bile and intestinal secretion. 

Following oral administration to animals, dichlorvos is rapidly absorbed from the digestive tract and extensively metabolized in the liver. The metabolism of dichlorvos has not been clearly elucidated because almost none of its potential metabolites has been yet unequivocally identified due mainly to its very rapid biotransformation rate (6). It appears, however, that the initial hydrolysis of dichlorvos, which occurs in all species, leads presumably to dichloroacetaldehyde (40), which is further metabolized by reduction to dichloroethanol or oxidation to dichloroacetic acid. In addition, dealkylation to desmethyldichlorvos appears to be another minor route of biotransformation, except in the mouse where desmethyldichlorvos constitutes at least 18% of the administered radioactivity. The metabolites of dichlorvos do not persist in tissues, whereas only trace levels occur in the milk of lactating mammals (41). There is no evidence tliat the metabolites of dichlorvos are toxic. 

Therapeutically used types of estrogens and prog-estins are listed in Tables 30-4 and 30-5. Both types of hormones can be administered in their natural form (estradiol and progesterone), and several synthetic derivatives of each type are also available. Most of the drugs listed in Tables 30-4 and 30-5 are available as oral preparations, and many conditions can be conveniently treated by oral administration. These hormones may also be administered transdermally via patches, creams, or gels the transdermal route may offer certain advantages, such as decreased side effects and liver problems.86,130 Certain preparations can be... 

Tin has been detected in rats after oral administration of 10 mg/kg/day tetralkyltin compounds (tetraethyltin, tetrapropyltin, and tetrabutyltin) (Iwai et al. 1982b). The compounds were found in the gastrointestinal tract, kidney and liver, while no retention was observed in brain and blood. The gastrointestinal tract retained primarily tetrapropyltin and tetrabutyltin. Levels (in pg tin/g wet tissue) were highest in the jejunum (5 and 4 pg tin/g, respectively). In the kidney, all 3 tetralkyltin compounds were found and levels ranged from 1 pg tin/g (tetrabutyltin) to less than 4 pg tin/g (tetraethyltin and tetrapropyltin). The liver retained primarily tetrabutyltin (approximately 2pg tin/g). The authors suggestion that the route, rate, and amount of excretion of the tetra- and trialkyltins depend on dialkylation, doses, physical and chemical properties, and route of administration appears reasonable. 

Toxicity data in animals indicated that similar effects occur after exposure to CDDs by oral, dermal, or parenteral routes. Toxicokinetic data in mice showed that 2,3,7,8-TCDD hepatic levels were similar following oral, intraperitoneal, and subcutaneous exposure (Nau and Bass 1981). However, recent data in rats showed that intratracheal administration of a 2,3,7,8-TCDD dose resulted in a relatively higher accumulation of 2,3,7,8-TCDD in the liver than after oral administration of the same dose (Diliberto et al. 1996). Intraperitoneal administration of 2,3,7,8-TCDD was less toxic than oral dosing in acute-exposure experiments with hamsters (Olson et al. 1980a). 

Estrogens are also subject to extensive first-pass effects (it has been shown that these first-pass effects occur predominantly in the intestinal wall, rather than in the liver) after oral administration. Again, vaginal administration of estradiol results in higher bioavailability than via the oral route (Figure 11 4(b)). 

Pharmacokinetics Procainamide [pro kane A mide] is absorbed following oral administration. [Note The intravenous route is rarely used because hypotension occurs if the drug is too rapidly infused.] Procainamide has a relatively short half-life of 2-3 hours. A portion of the drug is acetylated in the liver to N-acetylprocainamide (NAPA), which has little effect on the maximum polarization of Purkinje fibers but prolongs the duration of the action potential. Thus, NAPA has properties of a Class III drug. NAPA is eliminated via the kidney, and dosages of procainamide may need to be adjusted in patients with renal failure. 

Pharmacokinetics Sildenafil is rapidly absorbed after oral administration, and peak plasma levels are achieved within one hour. Bioavailability is about 40 percent of the oral dose. Sildenafil enters tissues, and has an apparent volume of distribution of 1.5 L/kg. Both sildenafil and its major N-desmethylated metabolite are > 95 percent bound to plasma proteins. Both CYP3A4 (major route) and CYP2C9 (minor route) are responsible for the metabolism of sildenafil. The major metabolite, N-desmethyl sildenafil, is approximately 50 percent as potent as sildenafil in inhibiting PDE5. The major route of elimination for sildenafil and its metabolites is via the bile. Clearance is decreased in older individuals free plasma concentrations are 40 percent higher in healthy volunteers > 65 years old. Severe renal impairment (< 30 mL/min) increases the AUC (see p. 7) by two-fold. Similarly, cirrhosis of the liver also significantly increases the AUC. 

Anesthetized rats are used for testing the side effect potential of a candidate compound on intermediary metabolism in liver, muscle and adipose tissue with subsequent effects on metabolic blood parameters (e.g. glucose, lactate, free fatty acids, triglycerides) and insulin. The use of anesthetized rats represents more a principal assessment of the pharmacological side effect potential since the candidate compound must be administered intravenously or intraperitoneally (enteral/intestinal administration should be avoided due to the anesthesia-induced decrease in intestinal motility with subsequent impairment of enteral absorption), compared to the study in conscious rats in which the candidate compound can be studied after oral administration, which in most cases represents the clinical route of administration for small molecular drugs. 

Conscious rats are used for testing the side effect potential of a candidate compound on intermediary metabolism in liver, muscle and adipose tissue with subsequent effects on metabolic blood parameters (e.g. glucose, lactate, free fatty acids, triglycerides) and insulin after oral administration, which represents in most cases the clinical route of administration for small molecular drugs. 

Animals. In rats, following oral administration, 92% was excreted in the urine and 5% in the feces within 24 hours. Residue levels in blood, liver, kidney, muscle, and fat tissues were <0.01 ppm after 48 hr Plants. Rapidly metabolized in non susceptible plants half-life in soya beans 1.6 days. The primary metabolic route in maize is oxidative hydroxylation at the carbon atom of the ethyl substituent on the pyridine ring... 

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