Distribution in body

The induction of systemic toxicity may involve a variety of complex interrelationships between the absorbed parent material, any conversion products, and their concentration and distribution in body tissues and fluids. The general pathway that a material may foUow after its absorption is shown schematically in Eigure 2. 

Cholesterol The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils, [nih]... 

Absorption/Distribution - Pyrazinamide is well absorbed from the Gl tract and attains peak plasma concentrations within 2 hours. It is widely distributed in body tissues and fluids including the liver, lungs, and cerebrospinal fluid. Pyrizinamide is approximately 10% bound to plasma proteins. Metabolism/Excretion - The half-life is 9 to 10 hours it may be prolonged in patients with impaired renal or hepatic function. 

The quinolones have long enjoyed a favorable pharmacokinetic profile. They are well absorbed and distributed in body tissues and fluids. A typical dose is between 100 mg and 1 g. The older agents have half-lives under 3 h, but a more typical value is between 4 and 14 h. Protein binding tends to be low to moderate (15-65%), but there are some exceptions such as nahdixic acid (90%) and garenoxacin (80%) (Howe and MacGowan, 2004). Bioavailability ranges from 55 to 100% (Dudley, 2003b). It has been well estabhshed in the hterature that the effectiveness of quinolones can be dramatically reduced if the medication is taken with an antacid. Many antacids are salts of divalent and trivalent cations such as Al " , Ca, and Mg " ". In addition, Fe " , Cu " , Ni " ", Zn " ", and also reduce quinolone activity. All these cations form a chelate with... 

Higher concentration of drugs that distribute in body fluids increased distribution and often prolonged elimination half-life of fat-soluble drugs... 

The quinolones are rapidly and almost completely absorbed after oral administration and are widely distributed in body tissues. Levels in extravascular spaces can often exceed serum levels. Levels lower than those found in serum occur in CSF, bone, and prostatic fluids. Ciprofloxacin and ofloxacin have been detected in breast milk and ofloxacin levels in ascites fluid are close to serum levels. Food ingestion does not affect bioavailability, which ranges from 50 to 95%. The half-life for most quinolones is 3 to 4 hours. 

Absorption from the intestinal tract is usually good. Food delays but does not reduce absorption. The drug is distributed in body fluids and has a half-Ufe of about 8 hours. High levels are found in plasma and cerebrospinal fluid (CSF). Less than 20% binds to plasma proteins. Metronidazole is metabolized by oxidation and glucuronide formation in the liver and is primarily... 

Pharmacokinetics Variable rate of absorption. Widely distributed in body tissues (eyes, kidneys, liver, lungs). Protein binding 45%. Partially metabolized in liver. Partially excreted in urine. Half-life 32 days (in plasma) 50 days (in blood). 

Pharmacokinetics Rapidly and completely absorbed from the GI tract food delays absorption. Protein binding 99%. Widely distributed in body tissues, including CNS. Extensively metabolized to active metabolites. Excreted in urine and eliminated in feces. Unknown if removed by hemodialysis. Half-life 2-4 hr. 

Decreased lean body mass distribute in body fluids increased... 

They are well absorbed from the GIT. They are widely distributed in body. Rate of entry into CNS is dependent on lipid solubility. Ultra short acting barbiturates are highly lipid soluble and quickly enter the brain. Redistribution to various tissues terminate their action and they are slowly released from the tissues and gradually metabolised in the liver. They are partly metabolised and partly excreted unchanged in urine. 

Chloramphenicol is completely absorbed after oral administration, bound to plasma protein (approximately 60%) and widely distributed in body. It crosses the blood-brain and placental barrier and shows its presence in CSF, bile and milk. It is conjugated with glucuronic acid in liver and excreted in urine. Small amount is excreted in urine in unchanged form. 

It is well absorbed from the GI tract, widely distributed in body. It is strongly plasma protein bound. It is metabolised in the liver to inactive metabolites which are excreted in the urine. 

Readily absorbed from the G1 tract, widely distributed in body tissues and fluids... 

Methanol can be absorbed through the skin or from the respiratory or gastrointestinal tract and is then distributed in body water. The primary mechanism of elimination of methanol in humans is by oxidation to formaldehyde, formic acid, and C02 (Figure 23-3). 

Quinine is derived from the bark of the cinchona tree, a traditional remedy for intermittent fevers from South America. The alkaloid quinine was purified from the bark in 1820, and it has been used in the treatment and prevention of malaria since that time. Quinidine, the dextrorotatory stereoisomer of quinine, is at least as effective as parenteral quinine in the treatment of severe falciparum malaria. After oral administration, quinine is rapidly absorbed, reaches peak plasma levels in 1-3 hours, and is widely distributed in body tissues. The use of a loading dose in severe malaria allows the achievement of peak levels within a few hours. The pharmacokinetics of quinine varies among populations. Individuals with malaria develop higher plasma levels of the drug than healthy controls, but toxicity is not increased, apparently because of increased protein binding. The half-life of quinine also is longer in those with severe malaria (18 hours) than in healthy controls (11 hours). Quinidine has a shorter half-life than quinine, mostly as a result of decreased protein binding. Quinine is primarily metabolized in the liver and excreted in the urine. 

Amoxicillin is widely distributed in body tissues and its metabolism is limited. Excretion of amoxicillin is tlirough the kidney, resulting in high concentrations in both the kidney tissue and urine, where the levels may be 100-fold higher than that in serum. Concentrations in milk are 10 times lower than those in serum. Following intramuscular or subcutaneous injection to goats, levels of amoxicillin in milk were very close to the detection limit of 10 ppb within 24 h after the last dose (65). 

Following injection, cephalothin is well and rapidly absorbed from intramuscular sites. It is widely distributed in body tissues and fluids and binds to plasma proteins. Cephalothin crosses the placenta and is found in breast milk. It... 

Cefoperazone is widely distributed in body tissues and fluids. It is bound to plasma proteins in the circulation. It is excreted primarily in the bile, and is also excreted in urine and poorly in breast milk. Cefoperazone is susceptible to the action of some -lactamases, and thus may be given with a -lactamase inhibitor. 

Distribution in the body is determined by the ability to penetrate membranous barriers (p. 20). Hydrophilic substances (e. g., in-ulin) are neither taken up into cells nor bound to cell surface structures and can thus be used to determine the extracellular fluid volume (2). Lipophilic substances diffuse through the cell membrane and, as a result, achieve a uniform distribution in body fluids... 

The distribution in body fluids of the different cystatins is remarkably different (Fig. 3). For example, while cystatin C is present in appreciable amounts in all investigated body fluids, cystatins S, SN, and SA are virtually confined to saliva, tears, and seminal plasma (Al). Cystatin D is present only in saliva and tear fluid (Al, F3). In some body compartments, e.g., spinal fluid, cystatin C represents more than 90% of the total molar concentration of cysteine protease... 

Pharmacokinetics and metabolism (ADMED Absorption into blood circulation Distribution in body MetaboUsm (= chemical reactions) of drug in the body Elimination of drug from body... 

Pharmacokinetics. Quinolones are well absorbed from the gut, and widely distributed in body tissue. Mechanisms of inactivation (hepatic metabolism, renal and biliary excretion) are detailed below for individual members. There is substantial excretion and re-absorption via the colonic mucosa, and patients with renal failure or intestinal malfunction, e.g. ileus, are prone to accumulate quinolones. 

Hyaluronic acid is a naturally occurring polysaccharide that is widely distributed in body tissues and intracellular fluids, including the aqueous and vitreous humour, synovial fluid, and in the ground substance that surrounds cells (1). It is a high-molecular weight substance originally developed for use as a vitreous replacement. Although 98% of the product consists of water, it is very viscoelastic. 

Amoxicillin is well absorbed when given orally, with a bioavailability that appears to be much higher than expected in the light of its physico-chemical properties and the pH partition theory [191], Numerous studies show recovery of intact amoxicillin in urine after oral administration in the range 43 to 80 % after 6 to 8 hours, with most figures in the upper part of this range [147,171,172,187,188,190]. An additional 10 to 25 % of the dose appears in urine as the penicilloic acid [147,148,152,171,172,187] with a ratio of about 2 to 1 of the 5R to 5S isomers [152,171,172]. Amoxicillin is extensively distributed in body tissues and fluids, with adequate levels for antibacterial activity in most of them [187,188,190], The half life in serum is about one hour and is the same for oral, intramuscular and intravenous administration [187,188,190]. Co-administration with potassium clavulanate does not affect the absorption, distribution and excretion of amoxicillin [190]. 

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