Liver blood

Systemie poisons attaek organs other than the initial site of eontaet. The eritieal organs are the kidneys, liver, blood and bone maiTow. 

A special case for reduced bioavailabilty results from first-pass extraction that sometimes might be subjected to saturable Michaelis-Menten absorption kinetics. The lower the hepatic drug clearance is (Clhep) in relation to liver blood flow (Ql), or the faster the drug absorption rate constant (Ka), and the higher the dose (D) are, the more bioavailable is the drug (F). 

Decreased liver blood flow decreased liver mass... 

It is important to monitor closely serum blood levels of chloramphenicol, particularly in patients with impaired liver or kidney function or when administering chloramphenicol with other drugs metabolized by the liver. Blood concentration levels exceeding 25 mcg/mL increase the risk of the patient developing bone marrow depression. 

Data from both in vivo and in vitro systems showed PbTx-3 to have an intermediate extraction ratio, indicating in vivo clearance of PbTx-3 was equally dependent upon liver blood flow and the activity of toxin-metabolizing enzymes. Studies on the effects of varying flow rates and metabolism on the total body clearance of PbTx-3 are planned. Finally, comparison of in vivo metabolism data to those derived from in vitro metabolism in isolated perfused livers and isolated hepatocytes suggested that in vitro systems accurately reflect in vivo metabolic processes and can be used to predict the toxicokinetic parameters of PbTx-3. 

Iturriage, H., Ugarte, H. and Israel, Y, (1980). Hepatic vein oxygenation, liver blood flow and the rate of ethanol metabolism in recently abstinent alcoholic patients. Eur. J. Clin. Invest. 10, 211-218. 

Hydrogen sulfide is widely distributed in the body. Sulfides have been found in the liver, blood, brain, lungs, spleen, and kidneys of humans who died after accidental inhalation exposure. 

Maximum binding capacity of erythrocytes Half-saturation concentration Partition coefficients for blood/tissue kinetics Blood/liver Blood/kidney... 

In man, the oral bioavailability of UK-224,671 is less than 10% [39]. Since clearance of UK-224,671 is low relative to liver blood flow, the poor oral bioavailability is due to incomplete absorption of the compound from the GIT. Caco-2 flux experi-... 

It was determined that 9.5% of an oral 80-mg dose of verapamil was absorbed in a 70-kg test subject. However, because of extensive bio transformation during its first pass through the portal circulation, the bio availability of verapamil was only 25%. Assuming a liver blood flow of 1500 mLAmin, the hepatic clearance of verapamil in this situation was... 

Some deaths. Residues (mg/kg fresh weight) >3 in brain, >10 in clotted heart blood, >6 in kidney, and up to 20 in liver Blood lead concentrations, in mg/L, increased from <0.1 at start to 0.1 after 24 h, 3.2 at 7 days, to 6.8 at 14 days. There were some deaths at day 21 and survivors had 0.6 mg Pb/kg blood FW. All dosed birds had immunosuppressive effects, as seen by lowered hemagglutination titers to sheep red blood cells... 

The rate of metabolism of nicotine can be determined by measnring blood levels after administration of a known dose of nicotine (Table 1) (Hukkanen et al. 2005c). Total clearance of nicotine averages about 1200 ml min . Nonrenal clearance represents about 70% of liver blood flow. Assuming most nicotine is metabolized by the hver, this means that about 70% of the drug is extracted from blood in each pass through the hver. 

An implication of the high degree of hepatic extraction is that clearance of nicotine should be dependent on liver blood flow. Thus, physiological events, such as meals, posture, exercise, or drugs perturbing hepatic blood flow, are predicted to affect the rate of nicotine metabolism. Meals consumed during a steady state infusion of nicotine result in a consistent decline in nicotine concentrations, the maximal effect seen 30-60 min after the end of a meal (Gries et al. 1996 Lee et al. 1989). Hepatic blood flow increases about 30% and nicotine clearance increases about 40% after a meal. 

Clearance of nicotine is decreased in the elderly (age >65) compared to adults (Molander et al. 2001). Total clearance was lower by 23%, and renal clearance lower by 49% in the elderly compared to yonng adults. Lower nicotine metabolism in the elderly may be contribnted to by rednced liver blood flow, since no decrease in CYP2A6 protein levels or nicotine metabolism in liver microsomes due to age has been detected (Messina et al. 1997). No differences in steady-state nicotine plasma levels or estimated plasma clearance valnes were detected in three age gronps (18-39, 40-59, and 60-69 years) nsing patches with the same nicotine content (Gonrlay and Benowitz 1996). The volnme of distribntion of nicotine is lower in older snbjects due to a decrease in lean body mass (Molander et al. 2001). 

The clearance of a drug is usually defined as the rate of elimination of a compound in the urine relative to its concentration in the blood. In practice, the clearance value of a drug is usually determined for the kidney, liver, blood or any other tissue, and the total systemic clearance calculated from the sum of the clearance values for the individual tissues. For most drugs clearance is constant over the therapeutic range, so that the rate of drug elimination is directly proportional to the blood concentration. Some drugs, for example phenytoin, exhibit saturable or dose-dependent elimination so that the clearance will not be directly related to the plasma concentration in all cases. 

Figure 4.1. Schematic representation of the architecture of the liver. Blood enters the liver through the portal vein (PV) and hepatic arteries (HA), flows through the sinusoids, and leaves the liver again via the central vein (CV). KC, Kupffer cells SEC, sinusoidal endothelial cells HSC, hepatic stellate cells BD, bile duct. Modified from reference 98.

Distribution. Quantitative inhalation, oral, or dermal distribution studies in humans are not available for 1,4-dichlorobenzene. 1,4-Dichlorobenzene has been detected in human blood, adipose tissue, and breast milk after an assumed inhalation exposure in Tokyo residents (Morita and Ohi 1975 Morita et al. 1975), as well as people in some parts of the United States (EPA 1983b, 1986). The available data indicate that after inhalation, oral, and subcutaneous exposure, 1,4-dichlorobenzene preferentially distributes to the fat tissue and organ-specific sites within the body (Hawkins et al. 1980), following the order adipose > kidney > liver > blood (Charboimeau et al. 1989b Hawkins et al. 1980). Although... 

In contrast to these concentrations many clinically-used drugs, which are non-inducers are effective at doses up to two orders of magnitude lower. The need for high doses has other undesirable complications. As outlined above dose size is important in toxicity and enzyme inducers show a high level of adverse drug reactions affecting such organs and tissues as the liver, blood and skin (Table 8.4). 

Some chemical exposures may be hepatic enzyme inducers/inhibitors, altering the effects of drugs like warfarin. Some foods such as mono-amines, will cause reactions in patients given MAOIs grapefruit juice may interact with terfenadine and some other drugs. New diseases may cause problems heart failure causing reduced liver blood flow can reduce the metabolism of drugs like warfarin. 

Sodium Ion. The excessive intake of sodium ion coming from other than NaCl should be noticed, though reduced intake of NaCl is now a matter of great concern. Monosodium glutamate (MSG), for instance, is a subject of discussion. Since MSG effectively provides umami taste, it has been very popular as a Japanese seasoning. In the United States, MSG has currently been mark as a cause of "Chinese restaurant syndrome". In addition, beef, liver, blood and their processed foods contains a large amount of sodium ion. Sine sodium ion combines with aspartic acid and glutamic acid residues in protein, study of affinity of acidic amino acids to sodium ion has to be set out first. 

Clearance, CLh Blood flow Fraction of drug Liver blood flow protein binding ... 

Wynne HA, Cope LH, Mutch E, et al. The effect of age upon liver volume and apparent liver blood flow in healthy man. Hepatology 1989 9 297-301. 

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