bluuebunny/crossref_metadata_2025_split huggingface dataset:
Investigation of 5‐FU disposition after oral administration of capecitabine, a triple‐prodrug of 5‐FU, using a physiologically based pharmacokinetic model in a human cancer xenograft model: comparison of the simulated 5‐FU exposures in the tumour tissue between human and xenograft model
Authors: Tsukamoto Yuko , Kato Yukio , Ura Masako , Horii Ikuo , Ishikawa Tohru , Ishitsuka Hideo , Sugiyama Yuichi 
Published: January 2005

AbstractThe nonlinear pharmacokinetics of capecitabine, a triple prodrug of 5‐FU preferentially activated in tumour tissues, was investigated in human cancer xenograft models. A physiologically based pharmacokinetic (PBPK) model integrating the activation process of capecitabine to 5‐FU and 5‐FU elimination was constructed to describe the concentration/time profiles of capecitabine and its three metabolites, including 5‐FU, in blood and organs. All the biochemical parameters (enzyme kinetic parameters, plasma protein binding and tissue binding of capecitabine and its metabolites) integrated in this model were measured in vitro. The simulated curves for the blood and tumour concentrations of capecitabine and its metabolites can basically describe the observed values. A simple prodrug of 5‐FU, doxifluridine, is known to be activated to 5‐FU to some extent in the gastrointestinal (GI) tract, causing diarrhoea, which is the dose limiting side effect of doxifluridine. Consequently, the therapeutic index (the ratio of 5‐FU AUC in the tumour to that in GI) after the administration of effective dose capecitabine was predicted by this PBPK model and found to be five times and 3000 times greater than that of doxifluridine and 5‐FU, respectively. This was compatible with the previous result for the difference in the ratio of the toxic dose to the minimum effective dose between capecitabine and doxifluridine, suggesting that 5‐FU preferentially accumulates in tumour tissue after oral administration of capecitabine compared with the other drugs (doxifluridine and 5‐FU). The 5‐FU AUC in tumour tissue of human cancer xenograft models at the minimum effective dose was comparable with those estimated for humans at the clinical dose. In addition, the predicted therapeutic indices at the respective doses were correlated well between humans and mice (xenograft model). These results suggest that the 5‐FU AUC in human tumour tissue at its clinically effective dose can be predicted based on the PBPK model inasmuch as the 5‐FU AUC in a human cancer xenograft model at its effective dose may be measured or simulated. Copyright © 2001 John Wiley & Sons, Ltd.
Transcellular transport of genistein, a soybean‐derived isoflavone, across human colon carcinoma cell line (Caco‐2)
Authors: Oitate Masataka , Nakaki Rie , Koyabu Noriko , Takanaga Hitomi , Matsuo Hirotami , Ohtani Hisakazu , Sawada Yasufumi 
Published: January 2005

AbstractGenistein, a soybean‐derived isoflavone, is thought to have an anticarcinogenic action, but little is known about the cellular mechanisms of its intestinal absorption. This study was designed to investigate the absorption mechanisms of genistein using human colon carcinoma cell line, Caco‐2 cells. The apical‐to‐basolateral transcellular transport of genistein across a Caco‐2 cell monolayer was significantly greater than that in the opposite direction. An uptake experiment revealed that cellular uptake of genistein by Caco‐2 cells was concentrative. The transcellular transport of genistein was saturable and temperature‐dependent, and was inhibited by other flavonoids such as rutin, quercetin, (+)‐catechin and (−)‐epicatechin. These results suggest that genistein is transported across Caco‐2 cells by a carrier‐mediated system, located on the apical membrane. Copyright © 2001 John Wiley & Sons, Ltd.
Effect of smoking on single dose pharmacokinetics of phenobarbital
Authors: Mirfazaelian A. , Jahanzad F. , Tabatabaei‐far M. , Farsam H. , Mahmoudian M. 
Published: January 2005

AbstractIn order to determine interaction of smoking with single dose pharmacokinetics of phenobarbital, a 60 mg tablet of the drug was given to 12 healthy male subjects in two groups (6 smokers and 6 non‐smokers) in a double blind study. An HPLC method using UV detection was developed to assess phenobarbital in plasma of the subjects. Pharmacokinetic parameters were calculated and compared in the two groups. Pharmacokinetic parameters of the two groups were not significantly different in the two groups (p<0.05). The results show no considerable effect of cigarette smoking on phenobarbital pharmacokinetics, which is in agreement with enzyme studies performed previously. Copyright © 2001 John Wiley & Sons, Ltd.
Angiotensin II receptor antagonist treatment during pregnancy
Authors: Alwan S. , Polifka J.E. , Friedman J.M. 
Published: January 2005

AbstractAngiotensin II (A‐II) is the main effector of the renin‐angiotensin system. A‐II functions by binding its type 1 (AT1) receptors to cause vasoconstriction and retention of sodium and fluid. Several AT1 receptor antagonists—a group of drugs collectively called “sartans”—have been marketed during the past few years for treatment of hypertension and heart failure. At least 15 case reports describe oligohydramnios, fetal growth retardation, pulmonary hypoplasia, limb contractures, and calvarial hypoplasia in various combinations in association with maternal losartan, candesartan, valsartan, or telmisartan treatment during the second or third trimester of pregnancy. Stillbirth or neonatal death is frequent in these reports, and surviving infants may exhibit renal damage. The fetal abnormalities, which are strikingly similar to those produced by maternal treatment with angiotensin‐converting enzyme (ACE) inhibitors during the second and third trimesters of pregnancy, are probably related to extreme sensitivity of the fetus to the hypotensive action of these drugs. Very little information is available regarding the outcome of human pregnancies in which the mother was treated with an AT1 receptor antagonist during the first trimester, but animal studies have not demonstrated teratogenic effects after maternal treatment with large doses of AT1 receptor antagonists during organogenesis. We conclude that pharmacological suppression of the fetal renin‐angiotensin system through ACE inhibition or AT1 receptor blockade seems to disrupt fetal vascular perfusion and renal function. We recommend that maternal treatment with AT1 receptor antagonists be avoided during the second and third trimesters of pregnancy and that women who become pregnant while taking one of these medications be changed to an antihypertensive drug of a different class as soon as the pregnancy is recognized. Birth Defects Research (Part A) 73, 2004. © 2004 Wiley‐Liss, Inc.
Analysis of lonidamine in rat serum and testis by high performance liquid chromatography
Authors: Grippa Eleonora , Gatto Maria Teresa , Leone Maria Grazia , Tita Beatrice , Adbel‐Haq Hanin , Vitalone Annabella , Silvestrini Bruno , Saso Luciano 
Published: January 2005

AbstractA HPLC method for the determination of lonidamine in serum and testis, suitable for pharmacological studies in the rat and other mammals, has been developed. Briefly, 0.5 mL of serum or about 0.2 g of testicular tissue were extracted with ethyl acetate and evaporated to dryness under nitrogen. The residue was redissolved in methanol and an aliquot was injected onto a C18 column eluted with a mobile phase consisting of acetonitrile:water (51:49, v/v), containing 0.1% trifluoroacetic acid. The eluate was monitored at 230 nm with a sensitivity of 0.05 AUFS. By this method, the pharmacokinetics and the serum and testicular levels of the drug up to 120 h after the administration of one single dose (100 mg/kg body weight) of lonidamine to Sprague–Dawley rats have been studied. Results were highly variable, as previously reported, but a very good linear correlation was found between the serum and the testicular levels, suggesting that, in the rat, and possibly in the human, testicular levels could be estimated based on the serum concentrations. Copyright © 2001 John Wiley & Sons, Ltd.
Abbreviations used:

ACN

acetonitrile

AUFS

absorbance units at full scale;

bw

body weight;

CV

coefficient(s) of variation;

EA

ethyl acetate;

HPLC

high performance units at full scale;

F

flurbiprofen;

LND

lonidamine;

NRS

normal rat serum;

NRT

normal rat testes;

NRTC

normal rat testicular cytosol;

P

peak area;

QC

quality controls;

S

serum;

TC

testicular cytosol;

TFA

trifluoroacetic acid.
Phenotype analysis of cytochrome P450 2C19 in Chinese subjects with mephenytoin S/R enantiomeric ratio in urine measured by chiral GC
Authors: Yao, T. W. , Zeng S. , Wang T. W. , Chen S. Q. 
Published: January 2005

AbstractA chiral gas chromatographic method with FID was developed for the determination of S‐ and R‐mephenytoin in human urine. The assay is linear from 25 to 800 ng/mL for each enantiomer and the limit of detection and limit of quantitation were 12 and 25ng/mL for each enantiomer, respectively. The method affords average recoveries of 74.41 ± 3.93% and 73.78 ± 3.02% for S‐ and R‐mephenytoin, respectively. The method allows the phenotype study of CYP2C19 in Chinese subjects. The phenotype pattern of 90 Chinese volunteers was determined, in which 26 volunteers received phenotyping and genotyping tests. The results of phenotype analysis showed that the interindividual variation was marked. The mephenytoin S/R enantiomeric ratios in urine of 11 volunteers were ≥0.95 and identified as poor metabolizers. The frequency of poor metabolizers was 12.2% in the Chinese subjects tested. A good relationship between phenotype and genotype analysis of CYP2C19 was observed. Copyright © 2001 John Wiley & Sons, Ltd.
Abbreviations used:

EM

extensive metabolizer

MP

mephenytoin

PM

Poor metabolizer
Determination of unbound cefamandole in rat blood by microdialysis and microbore liquid chromatography
Authors: Yeh Pen‐Ho , Lee Chi‐Hui , Cheng Fu‐Chou , Tsai Tung‐Hu 
Published: January 2005

AbstractTo analyze unbound cefamandole in rat blood, a method combing microdialysis with microbore liquid chromatography has been developed. A microdialysis probe was inserted into the jugular vein/right atrium of male Sprague–Dawley rats to examine the unbound cefamandole level in the rat blood following cefamandole administration (50 mg/kg, i.v.). The dialysates were directly submitted to a liquid chromatographic system. Samples were eluted with a mobile phase containing acetonitrile–methanol–100 mM monosodium phosphate (pH 5.0; 15:20:65, v/v). The UV wavelength was set at 270 nm for monitoring the analyte. Using the retrograde method, at infusion concentrations of 1 µg/mL of cefamandole, the in vivo microdialysis recoveries were 55.44% for the rat blood (n = 6). Intra‐ and inter‐assay accuracy and precision of the analyses were ≤10% in the range of 0.1–10 µg/mL. Pharmacokinetic parameters were calculated from the recovery‐corrected dialysate concentrations of cefamandole vs time data. The elimination half‐life (t1/2,β) was 21.6 ± 1.6 min. The results suggest that the pharmacokinetics of unbound cefamandole in blood following cefamandole administration (50 mg/kg, i.v., n = 5) fit best to the two‐compartmental model. Copyright © 2001 John Wiley & Sons, Ltd.
Abbreviations used:

RSD

relative standard deviation
Combination of HPLC and solid‐phase binding assay for isolation and purification of MHC class I and associated peptides using a bladder tumour cell line
Authors: Torabi‐Pour N. , Nouri A. M. E. , Perrett D. , Oliver R. T. D. 
Published: January 2005

AbstractThe major histocompatibility complex (MHC) class I molecules present processed self and non‐self peptides to T lymphocytes. Given that the class I peptide complex plays a critical role in cell‐mediated immunity, it is important to identify the nature of class I‐associated peptides unique to malignant cells as a prelude to the development of vaccines. The aim of this study was to combine immuno‐bead purification (using anti‐class I antibody W6/32) technique, sequential ultra‐filtration and high performance liquid chromatography (HPLC) to isolate class I antigens and associated peptides from an in‐house established bladder tumour cell line (Fen) whose missing class I antigens had been restored by β2‐microglobulin (β2‐m) gene transfaction. The results were as follows: (a) class I antigens could be separated from tumour cell lysate but only from the class I positive Fen cells; (b) treatment of CNBr‐W6/32 beads pre‐exposed to class I positive Fen lysate and eluted with dissociation agent (mild acid) resulted in the release of more than 20 peptides at an approximate molecular weight of between 700 and 3000 Da based on SDS–PAGE and silver staining analysis; (c) purified and eluted peptides from class I antigens showed distinct peaks when analysed by HPLC. The data presented in this investigation demonstrated the feasibility of isolating class I antigens and associated peptides from a bladder tumour cell line. The extension of these approaches to isolate peptides from tissue tumour biopsies may help the future of vaccine therapy in cancer patients. Copyright © 2001 John Wiley & Sons, Ltd.
Abbreviations used:

FCS

foetal calf serum

MHC

major histo compatibility complex

PAGE

polyacrylamide gel electrophoresis

RP

reverse‐phase

SDS

sodium dodecyl sulphate.
Separation of chiral 4‐substituted imidazole derivatives by cyclodextrin‐modified capillary electrophoresis†
Authors: Sasse Astrid , Schunack Walter , Stark Holger 
Published: January 2005

AbstractEnantiomeric separations by cyclodextrin‐modified capillary electrophoresis of chiral carbamates containing a 4‐substituted imidazole heterocycle, pharmacologically acting as histamine H3‐receptor antagonists, were carried out. Various cyclodextrins (α‐, β‐ and substituted β‐cyclodextrins) were investigated. Baseline resolution was achieved with six out of 11 compounds. Heptakis‐2,3,6‐trimethyl‐β‐cyclodextrin modified buffers seemed to be most efficient in separating most of the investigated compounds. The optical purity of one pair of enantiomers was determined. Copyright © 2001 John Wiley & Sons, Ltd.
Abbreviations used:

α‐CD

α‐cyclodextrin

β‐CD

β‐cyclodextrin

CD

cyclodextrins

CE

capillary electrophoresis

CM‐β‐CD

carboxymethylated‐β‐cyclodextrin

DM‐β‐CD

heptakis‐2,6‐dimethyl‐β‐cyclodextrin

DS

average degree of substitution

ee

enantiomeric excess

HE‐β‐CD

2‐hydroxyethyl‐β‐cyclodextrin

HP‐β‐CD

2‐hydroxypropyl‐β‐cyclodextrin

i.d.

inner diameter

LOD

limit of detection

LOQ

limit of quantification

Rs

resolution

SBE‐cd

sulphobutylether‐β‐cyclodextrin

SO4‐β‐CD

sulphated‐β‐cyclodextrin

TM7hyphen;β‐CD

heptakis‐2,3,6‐trimethyl‐β‐cyclodextrin
An LD50 model for predicting psychotropic drug toxicity using biopartitioning micellar chromatography
Authors: Quiñones‐Torrelo C. , Sagrado‐Vives S. , Villanueva‐Camañas R. M. , Medina‐Hernández M. J. 
Published: January 2005

AbstractThe LD50 determination is the main way to measure the acute toxicity of all types of substances. At the present time, however, there is increasing opposition to the use of living animals in research and testing activities from animal rights groups as well as some scientists. Nevertheless, the need to have a tool for estimating the potential toxicity of new compounds for human consumption has encouraged the development of alternative methods. Under adequate conditions, the partitioning in micellar liquid chromatography can describe the drug biopartitioning. We have named this chromatographic system biopartitioning micellar chromatography (BMC). In this paper, an LD50 QRAR model developed for psychotropic drugs from their retention data in BMC, is described. The model's ability to predict new psychotropic drug toxicity is statistically proved. Copyright © 2001 John Wiley & Sons, Ltd.
Abbreviations used:

BMC

biopartitioning micellas chromatography

QRAR

quantitative retention–activity relationships

QSAR

quantitative structure–activity relationships

RMSEC

root‐mean‐square error of calibration

RMSECV

root‐mean‐square error of cross‐validation.
Identification of reaction products of methamphetamine and hydrogen peroxide in hair dye and decolorant treatments by high‐performance liquid chromatography/mass spectrometry
Authors: Tanaka Seishi , Iio Reiko , Chinaka Satoshi , Takayama Nariaki , Hayakawa Kazuichi 
Published: January 2005

AbstractThe effect of hydrogen peroxide, a main component of hair dye and decolorant treatments, on methamphetamine (MA) was studied. Two analytical methods, thin‐layer chromatography (TLC) and high‐performance liquid chromatography/mass spectrometry (LC/MS), were used for the separation and identification of MA derivatives. Mixtures of MA solutions and hydrogen peroxide that had been incubated at 39°C for 24 h were shown to contain para‐hydroxy MA by TLC and para‐, meta‐ and ortho‐hydroxy MAs by LC/MS. In addition, MA N‐oxide and N‐hydroxy MA were found in MA/hydrogen peroxide mixtures immediately after mixing. Therefore, we concluded that MA changed to MA N‐oxide and N‐hydroxy MA before changing to para‐, meta‐ and ortho‐hydroxy MAs. Copyright © 2001 John Wiley & Sons, Ltd.
Abbreviations used:

AP

amphetamine

CID

collision‐induced dissociation

OHMA

hydroxy MA

MA

methamphetamine

TIC

total ion chromatogram
Determination of catecholamines and their 3‐O‐methyl metabolites in mouse plasma
Authors: Tsunoda Makoto , Takezawa Kazuko , Yanagisawa Teruyuki , Kato Masaru , Imai Kazuhiro 
Published: January 2005

AbstractThe determination of catecholamines and their 3‐O‐methyl metabolites in a single mouse plasma is necessary to understand the role of the sympathetic nervous activity, while the inactivation of catecholamines by catechol‐O‐methyltransferase indicates the activity of blood pressure regulation in animals. Here we report the basal catecholamines and their 3‐O‐methyl metabolite concentrations obtained from 15 µL of mouse plasma utilizing semi‐microcolumn high‐performance liquid chromatography (HPLC)‐peroxyoxalate chemiluminescence detection system. The concentrations were 6.63 ± 1.37 pmol/mL plasma, 0.49 ± 0.10 pmol/mL plasma, 5.25 ± 2.30 pmol/mL plasma, 3.23 ± 0.84 pmol/mL plasma, 0.44 ± 0.11 pmol/mL plasma, and 3.39 ± 1.67 pmol/mL plasma for norepinephrine, epinephrine, dopamine, normetanephrine, metanephrine and 3‐methoxytyramine, respectively (n = 5–7). Further, when blood pressure was reduced by minoxidil, plasma catecholamines were found to be significantly increased by the baroreflex‐mediated response in mouse. Copyright © 2001 John Wiley & Sons, Ltd.
Abbreviations used:

CA

catecholamine

COMT

catehol‐O‐methyltransferase

DA

dopamine

E

epinephrine

MN

metarephrines 3‐MT, 3‐methoxytyramine

NE

norepinephrine

NMN

normetanephrine

SHR

spontaneously hypertensive rats.

WKR

Wystar Kyoto rats.
Application of planar chromatography to the determination of cotinine in urine of active and passive smoking pregnant women
Authors: Tyrpień Krystyna , Bodzek Piotr , Mańka Grzegorz 
Published: January 2005

AbstractA quick and economical method for the determination of nicotine and its main metabolite‐cotinine in urine from smoking and passively smoking pregnant women is proposed using TLC‐densitometry. Chromatographic separations were performed on the plates coated with silica gel bound with C‐18 alkyl chains. Chromatograms were developed using a mixture of acetonitrile and water (88 + 12, v/v) in a horizontal chamber. Visualization was carried out under UV illumination at λ = 254 nm and then cotinine was quantified by the use of densitometer in reflectance mode at λ = 260 nm. Nicotine was identified after derivatization with Dragendorff reagent under visible light. The results of nicotine and cotinine analysis were verified by questionnaires obtained from pregnant women according to their age and smoking status correlated with spontaneous abortion frequency and child death rate. Copyright © 2001 John Wiley & Sons, Ltd.
Abbreviations used:

ETS

environmental tobacco smoke exposure
Analytical method of chondroitin/dermatan sulfates using high performance liquid chromatography/turbo ionspray ionization mass spectrometry: application to analyses of the tumor tissue sections on glass slides
Authors: Oguma Toshihiro , Toyoda Hidenao , Toida Toshihiko , Imanari Toshio 
Published: January 2005

AbstractWe established a highly sensitive quantitative analytical method for chondroitin/dermatan sulfates by LC/MS method. By this method, the unsaturated disaccharides produced after the enzymatic digestion of chondroitin/dermatan sulfates can be determined in the amounts as low as 0.5 pmol levels. The use of tetrabutylammonium hydroxide as an ion‐pair reagent for LC/MS allowed us to separate unsaturated 4‐sulfated disaccharide and unsaturated 6‐sulfated disaccharide. Furthermore, the peak areas of unsaturated disaccharides were increased almost 10 times by the postcolumn addition of acetonitrile. We applied this LC/MS method to the analyses of unsaturated disaccharides from chondroitin/dermatan sulfates in the tissues sections on glass slides, which were prepared from MethA tumor‐bearing mice. This method brought about considerable reduction in the time distance from sample collection to preparation of analytical results. Copyright © 2001 John Wiley & Sons, Ltd.
Abbreviations used:

ΔDi‐4S

2‐acetamido‐2‐deoxy‐3‐O‐(β‐D‐gluco‐4‐enopyranosyluronic acid)‐4‐O‐sulfo‐D‐galactose

ΔDi‐6S

2‐acetamido‐2‐deoxy‐3‐O‐(β‐D‐gluco‐4‐enopyranosyluronic acid)‐6‐O‐sulfo‐D‐galactose, ΔDiHS‐NS, 2‐deoxy‐2‐sulfamino‐4‐O‐(4‐deoxy‐α‐L‐threo‐hex‐4‐enopyranosyluronic acid)‐D‐glucose

TBAOH

tetrabutylammonium hydroxide

TPAOH

tetrapropionylammonium hydroxide
Development of predictive retention–activity models of butyrophenones by biopartitioning micellar chromatography
Authors: Martín‐Biosca Y. , Molero‐Monfort M. , Sagrado S. , Villanueva‐Camañas R. M. , Medina‐Hernández M. J. 
Published: January 2005

AbstractThe predictive and interpretative capability of quantitative chromatographic retention‐biological activity models is supported by the fact that in adequate experimental conditions the solute partitioning into the chromatographic system can emulate the solute partitioning into lipid bilayers of biological membranes, which is the basis of drug and metabolite uptake, passive transport across membranes and bioaccumulation. The use of retention data obtained in biopartitioning micellar chromatography (BMC) has been demonstrated to be helpful in describing the biological behaviour of different kinds of drugs. In this chromatographic system, polioxyethylene 23 lauryl ether Brij35 micellar mobile phases and C18 reversed stationary phase in adequate experimental conditions are used. The RP‐HPLC capacity factors of butyrophenones were determined using different Brij35 concentrations as micellar mobile phases. Relationships between seven biological activities of butyrophenones reported in bibliography and retention data were established and their predictive and interpretative ability evaluated. These relationships were significant between preclinical pharmacology and therapeutic efficacy parameters and the retention factors of butyrophenones (0.89 < R2 < 0.98). The results indicate that the retention of compounds in BMC is capable of describing and predicting in vitro the biological activities of butyrophenones. This approach can be very useful in the development of new neuroleptic drugs, avoiding the use of experimental animals. Copyright © 2001 John Wiley & Sons, Ltd.
Abbreviations used:

BMC

biopartitioning micellar chromatography

MLR

multiple linear regression

QRAR

quantitative retention–activity relationships

QSAR

quantitative structure–activity relationships

RMSEC

root mean square error of calibration

RMSECV

root mean square error of cross‐validation.