Protein plasma, binding

One of the plasma proteins which is mainly responsible for the plasma protein binding of drugs. Its level is known to be elevated in some pathological states, such as inflammation. 

The recommended dose of pemetrexed is 500 mg/m2 administered as an intravenous infusion over 10 min on Day 1 of each 21-day cycle. Pemetrexed is not metabolized to an appreciable extent and is primarily eliminated in the urine, with 70-90% of the dose recovered unchanged within the first 24 h following administration. Pemetrexed has a steady-state volume of distribution of 16.1 L. Pemetrexed is highly bound (approximately 81%) to plasma proteins. Binding is not affected by the degree of renal impairment. Plasma... 

Drug Interactions During Distribution Displacement from Plasma Protein Binding Sites... 

Benet LZ, Hoener BA (2002) Changes in plasma protein binding have little clinical relevance. Clin Pharmacol Ther 71(3) 115—121... 

Lombardo F, Obach RS, Shalaeva MY and Gao F. Prediction of volume of distribution values in humans for neutral and basic drugs using physicochemical measurements and plasma protein binding data. J Med Chem 2002 45 2867-76. 

Kratochwil NA, Huber W, Muller F, Kansy M and Gerber PR. Predicting plasma protein binding of drugs a new approach. Biochem Pharmacol 2002 64 1355-74. 

Lobell M and Sivarajah V. In silico prediction of aqueous solubility, human plasma protein binding and volume of distribution of compounds from calculated pKa and AlogP98 values. Mol Divers 2003 7 69-87. 

Certain other plasma proteins bind heme but not hemoglobin. Hemopexin is a Pj-globuhn that binds free heme. Albumin wiU bind some metheme (ferric heme) to form methemalbumin, which then ttansfets the metheme to hemopexin. 

The distribution of a drug in the body is largely driven by its physicochemical properties and in part for some compounds by the contribution of transporter proteins [17]. By using the Oie-Tozer equation and estimates for ionization (pfCj). plasma protein binding (PPB) and lipophilicity (log quite robust predictions for the volume of distribution at steady state (Vdss), often within 2-fold of the observed value, can be made [18]. 

Hansch and Leo [13] described the impact of Hpophihdty on pharmacodynamic events in detailed chapters on QSAR studies of proteins and enzymes, of antitumor drugs, of central nervous system agents as well as microbial and pesticide QSAR studies. Furthermore, many reviews document the prime importance of log P as descriptors of absorption, distribution, metabolism, excretion and toxicity (ADMET) properties [5-18]. Increased lipophilicity was shown to correlate with poorer aqueous solubility, increased plasma protein binding, increased storage in tissues, and more rapid metabolism and elimination. Lipophilicity is also a highly important descriptor of blood-brain barrier (BBB) permeability [19, 20]. Last, but not least, lipophilicity plays a dominant role in toxicity prediction [21]. 

Yamazaki, K., Kanaoka, M. Computational prediction of the plasma protein-binding percent of diverse... 

Avoid aspirin, as it may increase free T4 and T3 levels by interfering with plasma-protein binding ° Fluid resuscitation... 

L. Notarianni, Plasma protein binding of drugs in pregnancy and in neonates, Clin. Pharmacokinet, 18, 20 (1990). 

The aggregation and surface properties of Cardax, 3.19, in various aqueous formulations were comprehensively evaluated in 2005 (Foss et al. 2005c), as well as the potential plasma protein binding in mammalian applications with molecular modeling (Zsila et al. 2003). Cardax, 3.19, proved... 

The solubility of lysine derivative, 3.20, was measured at slightly over 180mg/mL, and molecular modeling also demonstrated potentially favorable plasma protein binding (Zsila et al. 2004). 

Zsila F, Fitos I, Bikadi Z, Simonyi M, Jackson HL, and Lockwood SF. 2004. In vitro plasma protein binding and aqueous aggregation behavior of astaxanthin dilysinate tetrahydrochloride. Bioorganic Medicinal Chemistry Letters 14(21) 5357-5366. 

Above 5 Low solubility and poor oral bioavailability. Erratic absorption. High metabolic liability, although potency may still be high. Basic amines tend to show high to very high Vd (Volume of distribution = ratio of overall tissue binding to plasma protein binding)... 

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