Competitive Displacement of Serum Protein Binding to Regulate Pharmacokinetics of a Corebral Blood Flow Radiopharmaceutical.
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Accession number;00A0997679
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| Title;Competitive Displacement of Serum Protein Binding to Regulate Pharmacokinetics of a Corebral Blood Flow Radiopharmaceutical. |
| Author;
KAWAI KEIICHI
(Miyazaki Med. Coll., Sch. of Med.)
TAKAMURA NORITO
(Miyazaki Med. Coll., Sch. of Med.)
NISHII RYUICHI
(Miyazaki Med. Coll., Sch. of Med.)
JINNOUCHI SEISHI
(Miyazaki Med. Coll., Sch. of Med.)
NAGAMACHI SHIGEKI
(Miyazaki Med. Coll., Sch. of Med.)
TAMURA SHOZO
(Miyazaki Med. Coll., Sch. of Med.)
ARIMORI KAZUHIKO
(Miyazaki Med. Coll., Sch. of Med.)
ODAGIRI MASAKI
(Kumamoto Univ., Fac. of Pharm. Sci.)
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Journal Title;Xenobiotic Metabolism and Disposition
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Journal Code:X0758A
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ISSN:0916-1139
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VOL.15;NO.Supplement;PAGE.S110-S111(2000)
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| Figure&Table&Reference;FIG.2, REF.5 |
| Pub. Country;Japan |
| Language;Japanese |
| Abstract;It is well-known that only free drug in blood is concerned with pharmacological activity. In case a therapeutic drug is administered with another displacer, which may displace competitively at the binding site of serum protein, the free fraction of this drug would be increased and consequently produce a high biological activity. So if the binding of radiopharmaceuticals to serum protein can be inhibited by displacers with high protein binding affinity, the total clearance and tissue distribution of this tracer would be enhanced. In this study, the interaction between 123I-labeled N-isopropyl-p-iodoamphetamine (123I-IMP) and several binding displacers was evaluated to improve cerebral imaging in rats and a monkey. The serum protein binding of 123I-IMP was evaluated by ultrafiltration. The free fraction rate of 123I-IMP was increased up to 1.2 times of control with albumin displacers. 6-Methoxy-2-naphtylacetic acid (6MNA), a clinically available HSA site II displacer, was selected for following studies. The rat biodistribution showed more rapid clearance of 123I-IMP with 6MNA loading. In scintigraphic study in rats, cerebral accumulation was slightly accelerated. It was also observed hasten cerebral accumulation in monkey dynamic scintigraphy. Indeed, 6MNA treatment increased free 123I-IMP in monkey serum study. Therefore, rapid and high cerebral accumulation was achieved. The displacement method could easily be applied to human study. The displacement of 123I-IMP binding on serum protein could shorten imaging time and reduce radiation dose for patients. Furthermore, in other radiopharmaceuticals with high protein binding, the competitive displacement on specific binding sites can control their tissue distribution and kinetics in clinical application. (author abst.) |
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