Drug-drug interactions due to protein binding. • Routes of Bioavailability/ bioequivalence absorption leads to systemic circulation . 17 Iron transport . Applications in toxicology: define the association between exposure. The less protein bound a drug is, the more efficiently it can pass between fluid compartments. The usual binding proteins are. Effective binding of iron is essential not only to ensure that it is available where Three key proteins regulate the transport and storage of iron. ..  reported a somehow better correlation between iron absorption and the.
Notably, the process of erythropoiesis, i. Accordingly, serum iron concentration and area under the curve AUC are clinically irrelevant for assessing iron utilization. Iron can be administered intravenously in the form of polynuclear iron III -hydroxide complexes with carbohydrate ligands or orally as iron II ferrous salts or iron III ferric complexes.
Several approaches have been employed to study the pharmacodynamics of iron after oral administration. Quantification of iron uptake from radiolabeled preparations by the whole body or the erythrocytes is optimal, but alternatively total iron transfer can be calculated based on known elimination rates and the intrinsic reactivity of individual preparations.
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Degradation kinetics, and thus the safety, of parenteral iron preparations are directly related to the molecular weight and the stability of the complex. High oral iron doses or rapid release of iron from intravenous iron preparations can saturate the iron transport system, resulting in oxidative stress with adverse clinical and subclinical consequences.
Appropriate pharmacokinetics and pharmacodynamics analyses will greatly assist our understanding of the likely contribution of novel preparations to the management of anemia. Introduction Iron is an essential component of every cell in the body. Although best known for its critical role in the transport and storage of oxygen in hemoglobin and myoglobin, respectivelywithin a large variety of enzymes iron also acts as a carrier for electrons, a catalyst for oxygenation, hydroxylation, and is necessary for cellular growth and proliferation.
Plasma protein binding
Iron supplements are widely administered to treat iron deficiency anemia, particularly in chronic diseases such as kidney disease [ 1 ], heart failure [ 2 ] or inflammatory bowel disease [ 3 ]. Without a sufficient supply of iron, hemoglobin cannot be synthesized and the number of erythrocytes in the blood cannot be maintained at an adequate level [ 4 ]. However, because of the ubiquity of iron, its compartmentalized sites of action, and its complex metabolism, usual pharmacokinetics measurements such as serum concentration are largely irrelevant when evaluating the bioavailability and efficacy of iron preparations [ 5 ].
As such, pharmacokinetics and pharmacodynamics assessments of iron preparations cannot be based on the standard principles that apply to non-endogenous drugs. Impact of the altered protein binding[ edit ] Only the unbound fraction of the drug undergoes metabolism in the liver and other tissues.
Plasma protein binding - Wikipedia
As the drug dissociates from the protein, more and more drug undergoes metabolism. Changes in the levels of free drug change the volume of distribution because free drug may distribute into the tissues leading to a decrease in plasma concentration profile. For the drugs which rapidly undergo metabolism, clearance is dependent on the hepatic blood flow. For drugs which slowly undergo metabolism, changes in the unbound fraction of the drug directly change the clearance of the drug.
The most commonly used methods for measuring drug concentration levels in the plasma measure bound as well as unbound fractions of the drug.Protein binding of drug
The fraction unbound can be altered by a number of variables, such as the concentration of drug in the body, the amount and quality of plasma protein, and other drugs that bind to plasma proteins.
Higher drug concentrations would lead to a higher fraction unbound, because the plasma protein would be saturated with drug and any excess drug would be unbound.
The Pharmacokinetics and Pharmacodynamics of Iron Preparations
If the amount of plasma protein is decreased such as in catabolismmalnutritionliver diseaserenal diseasethere would also be a higher fraction unbound. Additionally, the quality of the plasma protein may affect how many drug-binding sites there are on the protein.
Drug interactions[ edit ] Using 2 drugs at the same time can sometimes affect each other's fraction unbound.