Hepatic Local Disposition of a Drug with High Protein Binding and High Hepatic Clearance Using BOF-4272 as a Model Drug
スポンサーリンク
概要
- 論文の詳細を見る
The local disposition of a drug, which is efficiently eliminated by the liver in spite of very high binding with serum albumin, was investigated using BOF-4272 as a model drug in the hepatic perfusion system. Bovine serum albumin (BSA) labeled with Evans Blue was used as the marker of hepatic blood space. The perfusion experiments were carried out at 37℃ and at 4℃ to evaluate the local disposition in active and inactive livers, respectively. The perfusates included 0,0.25,0.5,1.0 and 4.0% of BSA in the injection of BOF-4272,and 0 and 1.0% of BSA in the injection of Evans Blue. After an instantaneous injection of BOF-4272 or Evans Blue (labeling reagent of BSA), the outflow time profile from the liver was analyzed by curve-fitting based on two-compartment dispersion model. All estimated parameters of BSA were almost the same between 37℃ and 4℃, which showed that the blood space in the liver was unaffected by perfusate temperature. The recovery ratio (F_H) and the mean transit time (t^^-_H) of BSA were 100% and about 0.1 min, respectively, both with BSA (1.0%) and without BSA in the perfusate. F_H of BOF-4272 increased from 20% to 50% with an increase in the perfusate BSA at 37℃, whereas F_H was almost constant (90%) regardless of BSA concentration at 4℃. t^^-_H of BOF-4272 was almost 0.1 min regardless of BSA concentration at 37℃, whereas t^^-_H decreased from 0.29 min to 0.17 min at 4℃ with an increase in the perfusate BSA. A large elimination (10%) of BOF-4272 was noticed even at 4℃ in the presence of perfusate BSA, which demonstrates that the passive transfer of BOF-4272 from BSA to the hepatic tissues is considerably rapid. This efficient transfer is responsible for the large hepatic clearance of BOF-4272 with very high binding with BSA.
- 公益社団法人日本薬学会の論文
- 1996-09-15
著者
-
NAITO Shinsaku
Research and Development Center, Otsuka Pharmaceutical Factory, Inc.
-
Nishimura M
Research And Development Center Otsuka Pharmaceutical Factory Inc.
-
Nishimura Masuhiro
Laboratory Of Drug Metabolism Research Naruto Research Institute Otsuka Pharmaceutical Factory Inc.
-
Nishimura Masuhiro
Department Of Drug Metabolism Division Of Pharmacology Drug Safety And Metabolism Otsuka Pharmaceuti
-
Yamada Kazushi
Department Of Pharmacy:department Of Internal Medicine Kyoto University Hospital Faculty Of Medicine
-
YAMAOKA Kiyoshi
Faculty of Pharmaceutical Sciences, Kyoto University
-
NAITO Shinsaku
Laboratory of Drug Metabolism Research, Naruto Research Institute, Otsuka Pharmaceutical Factory, In
-
NAKAGAWA Terumichi
Faculty of Pharmaceutical Sciences, Kyoto University
-
Naito S
Otsuka Pharmaceutical Factory Inc. Tokushima Jpn
-
Naito Shinsaku
Laboratory Of Drug Metabolism Research Naruto Research Institute Otsuka Pharmaceutical Factory Inc.
-
Nakagawa T
Graduate School Of Pharmaceutical Sciences Kyoto University
-
Yamaoka K
Moa Health Science Foundation Life Science Institute
-
Nakagawa Terumichi
Faculty Of Pharmaceutical Science Kyoto University
-
Yamaoka Kiyoshi
Faculty Of Pharmaceutical Science Kyoto University
関連論文
- Laser Ablation of Silk Protein (Fibroin) Films
- Pharmacological assessment of ARTCEREB_【○!R】 irrigation and perfusion solution for cerebrospinal surgery using primary cultures of rat brain cells
- Comparative analysis of ATP-binding cassette (ABC) transporter gene expression levels in peripheral blood leukocytes and in liver with hepatocellular carcinoma
- Cytochrome P450 gene expression levels in peripheral blood mononuclear cells in comparison with the liver
- Perfusion fluids used in neurosurgery affect cerebrospinal fluid and surrounding brain parenchyma in the rat ventriculocisternal perfusion model
- Effects of NO-1886 (Ibrolipim), a Lipoprotein Lipase-Promoting Agent, on Gene Induction of Cytochrome P450s, Carboxylesterases, and Sulfotransferases in Primary Cultures of Human Hepatocytes
- Influence of Albumin on Enantioselective Local Disposition of BOF-4272,a Xanthine Oxidase Inhibitor with Chiral Sulfoxide, in Rat Liver
- Hepatic Local Disposition of a Drug with High Protein Binding and High Hepatic Clearance Using BOF-4272 as a Model Drug
- カニクイザルにおける薬物代謝酵素およびトランスポーターmRNAの組織発現プロファイル
- ヒト組織におけるトランスポーター-SLC35ファミリーのmRNA発現プロファイル
- Comparison of Inducibility of Multidrug Resistance (MDR)1, Multidrug Resistance-Associated Protein (MRP)1, and MRP2 mRNAs by Prototypical Microsomal Enzyme Inducers in Primary Cultures of Human and Cynomolgus Monkey Hepatocytes(Pharmacology)
- Comparison of Inducibility of Sulfotransferase and UDP-Glucuronosyltransferase mRNAs by Prototypical Microsomal Enzyme Inducers in Primary Cultures of Human and Cynomolgus Monkey Hepatocytes
- One-Point サンプリングデータのブートストラップ法による薬物速度論パラメータのヒストグラム解析
- Soybean Oil Fat Emulsion to Prevent TPN-Induced Liver Damage : Possible Molecular Mechanisms and Clinical Implications
- Assessment of Induction of Cytochrome P450 by NO-1886 (Ibrolipim), a Lipoprotein Lipase-Promoting Agent, in Primary Cultures of Human Hepatocytes and in Female Rat Liver
- Major Role of Soybean Oil in Preventing Decrease in CYP4A1 mRNA Content Relative to PPARα mRNA Down-Regulation in Infant Rats(Pharmacology)
- Soybean Oil in Total Parenteral Nutrition Maintains Albumin and Antioxidant Enzyme mRNA Levels(Biopharmacy)
- Expression of Multidrug Resistance Proteins and Accumulation of Cisplatin in Human Non-small Cell Lung Cancer Cells(Biopharmacy)
- Role of Soybean Oil Fat Emulsion in the Prevention of Hepatic Xenobiotic Transporter mRNA Up- and Down-Regulation Induced by Overdose of Fat-free Total Parenteral Nutrition in Infant Rats
- Soybean Oil Fat Emulsion Prevents Cytochrome P450 mRNA Down-Regulation Induced by Fat-Free Overdose Total Parenteral Nutrition in Infant Rats(Biopharmacy)
- Effects of Pretreatment of Hep G2 Cells with β-Naphthoflavone on Cytotoxicity of Propranolol and its Active Metabolite 4-Hydroxypropranolol
- Effects of Dimethyl Sulfoxide on the Gene Induction of Cytochrome P450 Isoforms, UGT-Dependent Glucuronosyl Transferase Isoforms, and ABCB1 in Primary Culture of Human Hepatocytes
- 資料 Tissue Distribution of mRNA Expression of Human Cytochrome P450 Isoforms Assessed by High-Sensitivity Real-Time Reverse Transcription PCR
- Effects of Dimethyl Sulphoxide and Dexamethasone on mRNA Expression of Myogenesis- and Muscle Proteolytic System-related Genes in Mouse Myoblastic C2C12 Cells
- Preparation of a Novel Thin Film Utilizing a Magnetic Field : Alignment of Organic Microcrystals as Revealed by Atomic Force Microscopy
- Stereoselective Pharmacokinetics of BOF-4272 Racemate after Oral Administration to Rats and Dogs
- Preconcentration of Selenium by the Use of an Anion-Exchange Resin Loaded with Bismuthiol Derivatives (Proceedings of the 14th Symposium on Environmental Pollutants and Toxicology)
- Intrathecal Disposition of ARTCEREB® Irrigation and Perfusion Solution for Cerebrospinal Surgery in Rats
- On-Capillary Sample Preconcentration Incorporated in Chiral Capillary Electrophoresis
- MECHANISMS OF PHARMACOKINETIC INTERACTION BETWEEN AJMALINE AND QUINIDINE IN RATS
- A NONLINEAR MULTIPLE REGERSSION PROGRAM, MULTI2 (BAYES), BASED ON BAYESIAN ALGORITHM FOR MICROCOMPUTERS
- ヒトの肝細胞培養系を用いた新薬候補化合物曝露のCYP1A2およびCYP3A4誘導能の評価
- Enhancement of Myofibrillar Proteolysis Following Infusion of Amino Acid Mixture Correlates Positively with Elevation of Core Body Temperature in Rats
- Separation and Determination of Fluoride Ion by Using Ion Exchange Resin Loaded with Alizarin Fluorine Blue(Analytical,Chemical)
- Alteration of Propranolol Pharmacokinetics and Pharmacodynamics by Quinidine in Man
- POTENTIATION MECHANISM OF AJMALINE AND PROPRANOLOL ACTION BY QUINIDINE COADMINISTRATION
- Interactions between Local Anesthetics and Na^+ Channel Inactivation Gate Peptides in Phosphatidylserine Suspensions as Studied by ^1H-NMR Spectroscopy
- Analysis of gene and protein expression of cytochrome P450 and stress-associated molecules in rat liver after spaceflight
- Effects of Flower Arrangement and Flower Appreciation : Exhibition Study during Pacific Flora 2004
- Secretion of Albumin and Induction of CYP1A2 and CYP3A4 in Novel Three-dimensional Culture System for Human Hepatocytes using Micro-space Plate
- Induction of Human CYP1A2 and CYP3A4 in Primary Culture of Hepatocytes from Chimeric Mice with Humanized Liver
- Evaluation of Human CYP1A2 and CYP3A4 mRNA Expression in Hepatocytes from Chimeric Mice with Humanized Liver
- Enantioselective Uptake of BOF-4272, a Xanthine Oxidase Inhibitor with a Chiral Sulfoxide, by Isolated Rat Hepatocytes
- Introduction of Recirculatory Analysis into Portal and Systemic Concentration Difference Method
- Simultaneous Evaluation of Intestinal Absorption and Hepatic Extraction of 5-Fluorouracil Using Portal-Systemic Concentration Difference by Short-Period Double Dosing in a Single Conscious Rat
- A NONLINEAR LEAST SQUARES PROGRAM BASED ON DIFFERENTIAL EQUATIONS, MULTI (RUNGE), FOR MICROCOMPUTERS
- Effect of external Qi (MOA purifying therapy) on heart rate variability in climacteric women(International Conference on Mind Body Science : Physical and Physiological Approach joint with The Eighteenth Symposium on Life Information Science)
- HPLC DETERMINATION AND PHARMACOKINETIC INVESTIGATION OF CEPHALOSPORIN ANTIBIOTICS-DETERMINATION OF CEPHRADINE AND CEPHALEXIN IN BODY FLUIDS AND EFFECT OF FOOD INGESTION ON BIOAVAILABILITY OF CEPHALEXIN
- A NEW VERSION OF MULTI (ELS) FOR EXTENDED NONLINEAR LEAST SQUARES
- Consideration on Moments of Outflow Profile in Liver Perfusion System with Change in Perfusate Flow Rate Using Oxacillin as Model Drug
- PHARMACOKINETIC CONSIDERATION ON METABOLISM AND EXCRETION OF ISOXAZOLYLPENICILLINS IN MAN. COMPARISON OF FOUR ANALOGUES AND EFFECT OF COMBINED DOSE WITH AMPICILLIN
- COMPARATIVE PHARMACOKINETICS OF DICLOXACILLIN AND AMPICILLIN BETWEEN INDIVIDUAL AND COMBINED DOSES
- MOMENT ANALYSIS OF IN VIVO DISINTEGRATION, DISSOLUTION, AND ABSORPTION PROCESSES OF CEPHALEXIN PREPARATIONS IN MAN
- CORRELATION BETWEEN IN VIVO MEAN DISSOLUTION TIME AND IN VITRO MEAN DISSOLUTION TIME OF AMPICILLIN PRODUCTS
- A PHARMACOKINETIC ANALYSIS PROGRAM (MULTI) FOR MICROCOMPUTER
- Tissue-specific mRNA Expression Profiles of Human Nuclear Receptor Subfamilies
- Metabolic Pathways and Pharmacokinetics of BOF-4272,a Sulfoxide-Containing Drug, in the Dog : In Vivo and in Vitro Studies
- ALKALINE DEGRADATION OF CLAVULANIC ACID AND SULBACTAM, AND ITS APPLICATION TO HPLC DETERMINATION
- HPLC DETERMINATION AND PHARMACOKINETIC INVESTIGATION OF URINARY EXCRETION OF CLAVULANIC ACID
- Chromatographic Analysis and Pharmacokinetic Investigation of Cephaloglycin and Its Metabolites in Man
- Acidic Degradation of Cephaloglycin and High Performance Liquid Chromatographic Determination of Deacetyl-Cephaloglycin in Human Urine
- NMR studies on molecular interactions involved in alkali metal halide-amide-glycol ternary systems.