Human serum albumin (HSA) is a major protein component of blood plasma and plays an important role in the regulation of colloidal osmotic pressure, antioxidant capacity of human plasma, and the transport of numerous endogenous compounds such as fatty acids, hormones, toxic metabolites (e.g. bilirubin), bile acids, amino acids, and metals.1,2) The protein also binds a wide variety of drugs, [1][2][3] which has a significant impact on the pharmacokinetics and pharmacological effects of these drugs. 4,5) Free drug concentration can be affected by the presence of other drugs or endogenous compounds, or by microenvironmental changes in disease states. Diminished drug binding is usually the result of either competitive displacement from the same binding site or allosteric displacement following microenvironmental changes at the binding site. Several drugs bind with high affinity to one of the HSA sites 4,6) and these specific binding sites have been characterized since several decades. [7][8][9][10][11][12][13][14][15] Sudlow et al. 7,8) characterized two sites for drug binding, namely site I (also referred to as the warfarin binding site) and site II (the benzodiazepine binding site). Sjöholm et al. 9) have suggested the existence of one more binding site (the digitoxin site). The location of the latter site is largely unknown; however, crystallographic studies have assigned the location of sites I and II to subdomains IIA and IIIA of HSA, respectively. 3,10,11) This assignment of sites is supported by binding studies with fragments of HSA. [12][13][14][15] Since its first description by Wilmore and Dudrick in 1968, 16) parenteral nutrition has been an integral part of the medical management for a variety of patients who are in hypermetabolic states, or suffering from neurologic disease, gastrointestinal disease, cancer, and psychiatric illness. 17) This is because the nutrients required for humans; carbohydrates, fats, amino acids, electrolytes, vitamins, and trace minerals are considered to be available for use in parenteral feeding formulations.18,19) Despite the highly successful use of parenteral nutrition for several years, some adverse events have been reported, mostly regarding the errors in management of therapy using parenteral nutrition. 20) Most of the patients in whom parenteral nutrition is used, are also administered some therapeutic drugs, either orally, parenterally, or intravenously. The interaction between these drugs and the parenteral nutrition fluids may contribute to some cases of the adverse events. However, little information is available on the drug-parenteral nutrition fluid interaction, most notably with respect to the change in protein binding of the drug. [21][22][23][24][25] This study was undertaken to evaluate the effects of parenteral nutrition fluids, especially amino-acid fluids, on protein binding to drugs in vitro. The present findings on the interaction between amino-acid fluids and drugs were well explained based on the concept of binding sites. Kiyotake-cho, Miyazaki-...

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In quantifying of left ventricular function parameter, gated CMR provides similar quantitative values comparing with gated MPS except for ventricular volumes in rest conditions. In contrast, there were certain variations except for LVEF in exercised examinations. When we follow patients by the same cardiac parameters with CMR and MPS, using parameters across the two modalities proved to be possible under rest condition. However, it is limited at exercise condition.

When a therapeutic drug is competitively displaced at the binding sites of serum proteins, the free fraction of the drug will be increased, with an increase in the manifestation of pharmacologic properties. In the case of molecular imaging probes, total clearance and tissue distribution are increased in such circumstances. The aim of this study was to observe the increase in cerebral accumulation of N-isopropyl-p-123 I-iodoamphetamine ( 123 I-IMP) using the protein-binding displacement method with amino acid infusion. Methods: 123 I-IMP binding to human serum was investigated and identified. In addition, protein-binding sites and the specific binding sites of human serum albumin (HSA) and a 1 -acid glycoprotein (AGP) were examined by ultrafiltration. Then, serum-binding sites and the displacement effects of amino acid infusion, including Proteamin 12X Injection and Kidomin, were confirmed in vitro. Subsequently, displacement of 123 I-IMP serum protein binding with Proteamin amino acid infusion was tested in monkeys. A scintigraphic study of 123 I-IMP in monkeys loaded with or without Proteamin was performed, and timeactivity-curves of 123 I-IMP brain accumulation in monkeys were evaluated. Results: 123 I-IMP was bound to HSA site II and AGP to nearly equal extents. Compared with control conditions, loading with Proteamin and Kidomin markedly increased free fractions of binding site markers for HSA site II ( 14 C-diazepam: 0.95% 6 0.04% for control, 1.40% 6 0.06% for Proteamin, 1.62% 6 0.05% for Kidomin) and AGP ( 3 H-propranolol: 10.60% 6 0.32% for control, 13.18% 6 0.14% for Proteamin, 13.82% 6 0.72% for Kidomin). Amino acid infusions were thus suitable for use as displacers for binding site II and AGP. With use of Proteamin amino acid infusion to displace protein binding, the free fraction of 125 I-IMP (14.95% 6 0.74%) was significantly increased in serum (19.24% 6 0.87%). In a 123 I-IMP scintigraphic study of monkeys, average cerebral uptake in 2 monkeys increased by 1.34-fold with Proteamin. Our findings suggested that Proteamin treatment increased the free fraction of 123 I-IMP, yielding rapid and pronounced cerebral accumulation in vivo. Conclusion: Amino acid infusion can improve brain accumulation by competitive displacement of serum protein binding in vivo. Further similar studies are needed with other radiopharmaceuticals.