Abstract:
:Nafamostat mesilate, an ester drug with extensive hydrolysis in vivo, exhibits species difference in the relative contribution for its hydrolysis in blood and tissues. For the rat, the main hydrolysis site may be blood and human may be tissue (mainly by liver). The paper gave in vivo evidence that human tissue may give more contribution for its hydrolysis. In the initial phase of drug administration, the drug accumulating level in tissue was low; the efflux fraction from tissue into blood can be ignorable comparing with the drug influx into tissue. Based on urine and plasma metabolite analysis, we concluded that in the initial phase almost all the drug hydrolysis in blood was excreted into urine. Then according to the initial urine metabolite analysis, we can estimate the drug hydrolysis rate in blood. The rate of drug diffusion from blood into tissues can be deduced based on the mass balance analysis of the initial blood drug. With the estimated rate constants, the drug efflux from tissues into blood was calculated according to equation: OFT-B (efflux from tissues) = OFB-U (blood hydrolysis fraction)+OFB-T (influx into tissues)-DB (hydrolysis in blood). The net flow (influent flux minus effluent flux) represented the drug hydrolysis fraction in tissue. As the result indicated, in human about 20% drug administrated was hydrolyzed in blood and nearly 80% in tissues. The relative hydrolysis fraction indicated that the main hydrolysis site in human body may locate in tissue, which was different to rats.
journal_name
Biol Pharm Bulljournal_title
Biological & pharmaceutical bulletinauthors
Cao YG,Chen YC,Hao K,Zhang M,Liu XQdoi
10.1248/bpb.31.1985subject
Has Abstractpub_date
2008-11-01 00:00:00pages
1985-9issue
11eissn
0918-6158issn
1347-5215pii
JST.JSTAGE/bpb/31.1985journal_volume
31pub_type
杂志文章abstract::The effect of carboxamidemethylated Fc fragment (CM-Fc) from human immunoglobulin G (IgG) on type II collagen (C II)-induced arthritis (CIA) in DBA/1J mice was studied. CM-Fc suppressed the development of CIA while Fc fragment did not. CM-Fc inhibited the increase in serum anti-C II IgG. CM-Fc suppressed C II-induced ...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.17.623
更新日期:1994-05-01 00:00:00
abstract::The present study was performed to investigate the effects of histamine H(1)-antagonists on the sleep-awake state in rats placed on a grid suspended over water in comparison with rats placed on sawdust. When rats were placed on the grid suspended over water, significant increases in the awake time and decreases in non...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.32.51
更新日期:2009-01-01 00:00:00
abstract::The purpose of this study was to investigate the characteristics of arachidonic acid-induced peripheral vascular disease in rats. Injecting arachidonic acid (2 mg/leg) into the femoral artery caused hind limb gangrene. Histopathological examination revealed occlusive thrombi and marked vascular injury, including denud...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.22.257
更新日期:1999-03-01 00:00:00
abstract::Despite the relatively high prevalence of migraine or headache, the pathophysiological mechanisms triggering headache-associated peripheral hypersensitivities, are unknown. Since nitric oxide (NO) is well known as a causative factor in the pathogenesis of migraine or migraine-associated hypersensitivities, a mouse mod...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.b17-00589
更新日期:2018-02-01 00:00:00
abstract::Eight new diterpenoids (1-8) have been isolated from the wood of Excoecaria agallocha (Euphorbiaceae) and their inhibitory effects on the induction of Epstein-Barr virus early antigen (EBV-EA) in Raji cells were examined to search for potent anti-tumor-promoters from natural resources. Of these compounds, the secolabd...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.24.1440
更新日期:2001-12-01 00:00:00
abstract::We examined the influence of 8-hydroxy-2-di-n-propylamino tetralin (8-OH-DPAT), a serotonin 1A (5-HT1A) receptor full agonist, on the wet-dog shake response induced by the (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), a 5-HT2A receptor agonist, in adrenocorticotropic hormone (ACTH)-treated rats. Chronic A...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.30.117
更新日期:2007-01-01 00:00:00
abstract::Novel delivery technology using cell-penetrating peptides (CPPs) have recently shown their potential and are emerging as promising candidates for an oral protein and peptide delivery systems. As with for the development of any absorption enhancer that is meant to function across an epithelial layer covering a surface ...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.b14-00517
更新日期:2015-01-01 00:00:00
abstract::The induction of a mutant DnaA protein (DnaA E204Q) with decreased intrinsic ATPase activity in cells causes a lethal phenotype. Based on our results that the decreased ATPase activity of DnaA E204Q is activated to the level of a wild-type protein in the presence of partially purified stimulating factors for DnaA ATPa...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.22.904
更新日期:1999-09-01 00:00:00
abstract::Fusion peptide P-9 was isolated from bovine serum albumin by controlled pepsin degradation in the presence of caprylic acid, followed by Sephadex G-75 gel filtration and ion-exchange chromatography of CM-cellulose. By this procedure, P-9 could be strictly separated from peptic fragment P-Phe, which has a molecular wei...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.22.1360
更新日期:1999-12-01 00:00:00
abstract::A current anti-inflammatory agent often targets the prevention of inflammatory disorder development. The standardized Centella asiatica ECa 233 extract has been previously reported for anti-inflammatory effect. This study aimed to investigate its anti-inflammatory effect and mechanisms of ECa 233 in lipopolysaccharide...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.b19-00248
更新日期:2019-01-01 00:00:00
abstract::The extracellular matrix (ECM), which contributes to structural homeostasis as well as to the regulation of cellular function, is enzymatically cleaved by proteases, such as matrix metalloproteinases and cathepsins, in the normal and diseased heart. During the past two decades, matricryptins have been defined as fragm...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章,评审
doi:10.1248/bpb.b17-00308
更新日期:2017-01-01 00:00:00
abstract::Cloning of polyketide synthase (PKS) gene for amphidinolide biosynthesis was attempted from a dinoflagellate Amphidinium sp. (strain Y-42). Fourteen beta-ketoacyl synthase gene fragments were obtained by Polymerase Chain Reaction (PCR) amplification from degenerated primer sets designed on the basis of the conserved a...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.29.1314
更新日期:2006-07-01 00:00:00
abstract::The effects of conjugated linoleic acid (CLA) against anaphylaxis and allergic pruritus were investigated using a in vivo assay. Inhibitory effects of CLA were observed on the immediate (type 1) hypersensitivity reaction, with CLA significantly suppressing the decrease in blood pressure (BP) and blood flow (BF) induce...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.25.1655
更新日期:2002-12-01 00:00:00
abstract::Several neurological disorders such as Alzheimer's and Parkinson's diseases have been attributed to gamma-aminobutyric acid (GABA) depletion in the brain. In order to provide a pharmacological basis for the neuroprotective actions of the enhanced accumulation of GABA in mulberry leaves (ML) against cerebral ischemia i...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.29.270
更新日期:2006-02-01 00:00:00
abstract::Berberine is an isoquinoline plant alkaloid with a long history of being used for the treatment of many diseases in Chinese herbal medicine. Berberine has a wide range of biochemical and pharmacological effects, including antitumor activities, but its mechanism of action is not clearly understood. In this study, we in...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.31.558
更新日期:2008-04-01 00:00:00
abstract::The degradation of 125I-endothelin-1 (125I-ET-1) was examined on cultured porcine aortic endothelial cell (EC) and rat vascular smooth muscle cell (SMC) by HPLC analysis. The degradation of ET-1 was observed on SMC and was slightly observed on EC. Membrane fractions of SMC had a strong potency for the degradation of E...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.17.376
更新日期:1994-03-01 00:00:00
abstract::The bioavailability of morphine after rectal administration using three types of suppositories containing morphine hydrochloride (10 mg) in different added forms was evaluated in rabbits. Three types of suppositories were constructed with a base material (Witepsol H-15): a conventional suppository containing morphine ...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.16.150
更新日期:1993-02-01 00:00:00
abstract::We have isolated insulin resistant mice (ddY-H mice) which are spontaneously induced even if fed with the standard chow pellets. Since marked accumulation of triglycerides (TG) in liver was observed, the present study investigated causes of hepatic TG accumulation in ddY-H mice fed with the standard chow pellets. In d...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.b12-01000
更新日期:2013-01-01 00:00:00
abstract::Diosgenyl saponins are the most abundant steroid saponins, and exert a large variety of biological functions. In a previous report, we showed that dioscin was able to induce cytotoxicity and apoptosis in human myeloblast leukemia HL-60 cells. This study further investigated the action mechanisms underlying this effect...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.27.1059
更新日期:2004-07-01 00:00:00
abstract::Sec61β is the β subunit of the Sec61 translocon and is responsible for expression and delivery of basolateral membrane proteins, including claudins, major constituents of tight junction (TJ). In the present study, the effect of Sec61β overexpression on TJ barrier functions in Madin-Darby canine kidney (MDCK) cells wer...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.b13-00936
更新日期:2014-01-01 00:00:00
abstract::Aconitine administered intraperitoneally (i.p.) produces bradycardia mainly by a central muscarinic action. The involvement of hypothalamic regions in the occurrence of aconitine-induced bradycardia was investigated in hypothalamus-lesioned mice. The lesions were made by passing a direct current (1.5 mA, 13 s) through...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.20.856
更新日期:1997-08-01 00:00:00
abstract::The mitochondrial ADP/ATP carrier (AAC) has 6 transmembrane regions and 3 matrix loops. Our previous mutational study on the Cys residue in the LM1s of chimeric bovine type 1 AAC (yN-bAAC1), in which the N-terminal 11 amino acids of bovine type 1 AAC are substituted with the corresponding 26 amino acids of yeast type ...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.30.885
更新日期:2007-05-01 00:00:00
abstract::To elucidate molecular mechanisms of adipocyte differentiation, we previously isolated TC10-like/TC10betaLong (TCL/TC10betaL), regulators of G protein signaling 2 (RGS2), factor for adipocyte differentiation (fad) 104 and fad158, which were transiently expressed in the early phase of adipogenesis. These four genes see...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.33.404
更新日期:2010-01-01 00:00:00
abstract::The effect of pulsed output ultrasound (1 MHz) with on/off ratios of 1:2, 1:4 and 1:9 on transdermal absorption of indomethacin from an ointment was studied in rats. Ultrasound energy was supplied for between 10 and 19 min at a range of intensities (1.0-2.5 W.cm-2), energy levels commonly used for therapeutic purposes...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.20.288
更新日期:1997-03-01 00:00:00
abstract::Accumulation of β-amyloid peptide (Aβ) in the brain plays an important role in the pathogenesis of Alzheimer’s disease (AD). Previous studies have demonstrated the neuroprotective role of osthole against oxygen and glucose deprivation in cortical neurons. However, the effects of osthole on Aβ-induced neurotoxicity in ...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.b13-00561
更新日期:2013-01-01 00:00:00
abstract::The antiproliferative constituents in the MeOH extracts of the aerial parts of Lippia dulcis Trev. and Lippia canescens Kunth (Verbenaceae) were investigated. Activity-guided chemical investigation of the MeOH extracts resulted in the isolation of the three bisabolane-type sesquiterpenes [(+)-hernandulcin (1), (-)-epi...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.25.920
更新日期:2002-07-01 00:00:00
abstract::Recent studies have shown that antibodies with low fucose content in their oligosaccharides exhibit highly potent antibody-dependent cellular cytotoxicity (ADCC). However, composites of therapeutic antibodies produced by conventional production systems using cell lines such as Chinese hamster ovary (CHO) and SP2/0 do ...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.32.1604
更新日期:2009-09-01 00:00:00
abstract::Compound C is a widely used chemical inhibitor that down-regulates AMP-activated protein kinase (AMPK) activity. However, it has been suggested that compound C exerts AMPK-independent effects in various cells. Here, we investigated whether compound C induces Sestrin2 (SESN2), an antioxidant enzyme induced by diverse s...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.b15-00938
更新日期:2016-01-01 00:00:00
abstract::Two angiotensin-I-converting enzyme (ACE) inhibitory peptides were isolated from a tryptic hydrolysate of human serum albumin (HSA). The peptides were identified by sequencing and other analyses as Ala-Trp and the nonapeptide Ala-Phe-Lys-Ala-Trp-Ala-Val-Ala-Arg (human albutensin A), corresponding to f(213-214) and f(2...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.23.879
更新日期:2000-07-01 00:00:00
abstract::We used three human urological cancer cell lines, PC-3, LNCaP and SKRC-1, to investigate the effects of the extract from Serenoa repens (Palmae) on tumor cell invasion. The invasion activity of these cell lines was determined in vitro using a Transwell cell-culture chamber. The invasion activity of PC-3 cells into Mat...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.24.188
更新日期:2001-02-01 00:00:00