Kidney plasma protein binding

Plasma protein binding is 99.8%. It is extensively distributed into tissues that are prone to fungal invasion. Concentrations in the lung, kidney, liver, bone, stomach, spleen, and muscle were found to be 2 to 3 times higher than the corresponding plasma concentration. Following IV administration, the volume of distribution averaged 796 185 L. 

Teicoplanin, like vancomycin, is not absorbed from the intestinal tract. Peak plasma levels are achieved about 2 hours after intramuscular administration. The drug distributes widely in tissues plasma protein binding is about 90%. The half-Ufe approximates 50 hours, which is considerably longer than that of vancomycin, and may make it useful for outpatient administration. Like vancomycin, teicoplanin is excreted by the kidneys. 

This is known as Michaelis-Menten or saturation kinetics. The processes that involve specific interactions between chemicals and proteins such as plasma protein binding, active excretion from the kidney or liver via transporters, and metabolism catalyzed by enzymes can be saturated. This is because there are a specific number of binding sites that can be fully occupied at higher doses. In some cases, cofactors are required, and their concentration may be limiting (see chap. 7 for salicylate, paracetamol toxicity). These all lead to an increase in the free concentration of the chemical. Some drugs, such as phenytoin, exhibit saturation of metabolism and therefore nonlinear kinetics at therapeutic doses. Alcohol metabolism is also saturated at even normal levels of intake. Under these circumstances, the rate of... 

Clearance may also be viewed as the loss of drug from an organ of elimination such as the liver or kidney. This approach enables evaluation of the effects of a variety of physiological factors such as changes in blood flow, plasma protein binding, and enzyme activity. Therefore, total systemic clearance is determined by adding the clearance (CL) values for each elimination organ or tissue ... 

Due to the small size (smaller than lOkD in most cases), oligonucleotide can be easily filtered at the kidney. In addition, its properly of plasma protein binding will greatly alter the biodistribution of oligonucleotides. Compared with natural phosphodiester oligonucleotide, the phosphorothioate one has a... 

In terms of ADMET, following oral administration about half of the atenolol dose is absorbed. Plasma-protein binding is minimal (3-5%). Peak plasma concentrations, as well as peak action, are reached in 2-4 h. Atenolol has low lipid solubility, and only small amounts cross the blood-brain barrier. Thus, atenolol s CNS side effects are less than with other beta-blockers [75]. Atenolol is excreted mainly by the kidneys, with little or no hepatic metabolism. It crosses the placenta, and concentrations in breast milk can be similar or even higher than those in maternal blood [76]. Atenolol is not recommended in asthma, even though its high beta-1 selectivity makes it safer in obstructive pulmonary disease than nonselective beta-blocking agents. Atenolol s important ADMET characteristics are listed in Tab. 8.2. 

Chloroquine is absorbed rapidly and almost completely from the gut peak serum concentrations are attained within 1 or 2h. Chloroquine plasma protein binding is 55%. Its volume of distribution is 116-2851 kg The drug may be found in 500 times greater concentration within the liver, spleen, kidneys, lungs, and leukocytes (compared with plasma). Chloroquine appears to cross the placenta readily. A very small amount is transmitted into breast milk. 

After absorption, meprobamate can be found throughout the body and has a volume of distribution of 0.75 lkg . Plasma protein binding is 15%. It is excreted by the kidneys either in its unchanged form (10%) or as inactive metabolites. 

Studies of the distribution of [3H]ginsenoside Rgl following intravenous injection have been performed in mice (80). Tissue radioactivity was greatest in the kidney, followed by the adrenal gland, liver, lungs, spleen, pancreas, heart, testes, and brain. Plasma protein binding was 24%, and tissue protein binding was 48% in the liver, 22% in testes, and 8% in the brain. 

Nicotine has low plasma protein binding (<5%) and a large volume of distribution (2-3 L/kg). It is eliminated mainly by hepatic metabolism, although some metabolism occurs in the lungs and kidneys. The main metabolites are cotinine (15% of the dose) and trans-3-hy-droxycotinine (45% of the dose). Only 10% of the absorbed dose is excreted unchanged in urine. In healthy adult smokers, nicotine has an apparent elimination half-life of 1-2 h and the average plasma clearance is 1.2 h (93). 

Lipid-soluble drugs enter cells readily. Distribution of such drugs is widespread unless plasma protein binding is extensive. Elimination of lipid-soluble drugs is usually slow because clearance from plasma via the kidneys removes only a small proportion of the drug in any given time. 

Explain the importance of plasma protein binding to absorption of a drug from the gastrointestinal tract, its distribution around the body and its excretion by the kidneys. 

Variation in response to drug therapy can occur due to many factors. At extremes of life absorption, distribution, metabolism and excretion can all be different to normal so that drug action becomes unpredictable. In particular, plasma protein binding, liver and kidney function and the number of drugs being taken concurrently become important in older patients. 

Toxicity The toxic effects of sulfonamides include skin rashes, gastrointestinal distress, hemolysis, kidney damage, and drug interactions caused by competition for plasma protein binding sites. Pyrimethamine may cause folic acid deficiency when used in high doses. 

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