当前位置： SCI文献检索 > EUROPEAN JOURNAL OF DRUG METABOLISM AND PHARMACOKINETICS期刊下所有文献 > Physiologically based modeling of lisofylline pharmacokinetics following intravenous administration in mice.

Physiologically based modeling of lisofylline pharmacokinetics following intravenous administration in mice.

Abstract：

:Lisofylline (LSF), is the R-(-) enantiomer of the metabolite M1 of pentoxifylline, and is currently under development for the treatment of type 1 diabetes. The aim of the study was to develop a physiologically based pharmacokinetic (PBPK) model of LSF in mice and to perform simulations in order to predict LSF concentrations in human serum and tissues following intravenous and oral administration. The concentrations of LSF in serum, brain, liver, kidneys, lungs, muscle, and gut were determined at different time points over 60 min by a chiral HPLC method with UV detection following a single intravenous dose of LSF to male CD-1 mice. A PBPK model was developed to describe serum pharmacokinetics and tissue distribution of LSF using ADAPT II software. All pharmacokinetic profiles were fitted simultaneously to obtain model parameters. The developed model characterized well LSF disposition in mice. The estimated intrinsic hepatic clearance was 5.427 ml/min and hepatic clearance calculated using the well-stirred model was 1.22 ml/min. The renal clearance of LSF was equal to zero. On scaling the model to humans, a good agreement was found between the predicted by the model and presented in literature serum LSF concentration-time profiles following an intravenous dose of 3 mg/kg. The predicted LSF concentrations in human tissues following oral administration were considerably lower despite the twofold higher dose used and may not be sufficient to exert a pharmacological effect. In conclusion, the mouse is a good model to study LSF pharmacokinetics following intravenous administration. The developed PBPK model may be useful to design future preclinical and clinical studies of this compound.

journal_name

Eur J Drug Metab Pharmacokinet

journal_title

European journal of drug metabolism and pharmacokinetics

authors

Wyska E,Świerczek A,Pociecha K,Przejczowska-Pomierny K

doi

10.1007/s13318-015-0260-y

subject

Has Abstract

pub_date

2016-08-01 00:00:00

pages

403-12

issue

4

eissn

0378-7966

issn

2107-0180

pii

10.1007/s13318-015-0260-y

journal_volume

41

pub_type

杂志文章

相关文献

EUROPEAN JOURNAL OF DRUG METABOLISM AND PHARMACOKINETICS文献大全
  • Irreversible binding to proteins after single and repeated daily oral administration of 4-(2,2-diphenylethyl) imidazole (SC-46264) to the Cynomolgus monkey.

    abstract：:SC-46264 is an antagonist of the alpha 2-adrenergic receptor. Distribution and excretion of [14C]-SC-46264 were studied after single and repeated daily oral administrations to the Cynomolgus monkey at a 1.5 mg/kg dose. After a single oral administration, more than 95% of the administered dose was recovered within 48 h...

    journal_title：European journal of drug metabolism and pharmacokinetics

    pub_type： 杂志文章

    doi：10.1007/BF03188812

    authors： Jacqmin P,Hérin M,Cavalier R,Lesne M

    更新日期：1993-07-01 00:00:00

  • Supramolecular Complex of Ibuprofen with Larch Polysaccharide Arabinogalactan: Studies on Bioavailability and Pharmacokinetics.

    abstract：BACKGROUND AND OBJECTIVES:In the present work, pharmacological and pharmacokinetic properties of the supramolecular complex of non-steroid anti-inflammatory drug ibuprofen (IBU) with natural polysaccharide arabinogalactan (AG) were studied. The main goals of such complexation were the increase of ibuprofen's bioavailab...

    journal_title：European journal of drug metabolism and pharmacokinetics

    pub_type： 杂志文章

    doi：10.1007/s13318-016-0357-y

    authors： Khvostov MV,Borisov SA,Tolstikova TG,Dushkin AV,Tsyrenova BD,Chistyachenko YS,Polyakov NE,Dultseva GG,Onischuk AA,An'kov SV

    更新日期：2017-06-01 00:00:00

  • Effects of silymarin on the pharmacokinetics of atorvastatin in diabetic rats.

    abstract：:The effect of silymarin (SMN) on the pharmacokinetics of atorvastatin in diabetic rats was evaluated. Male Wistar rats were assigned into two major groups and then sub-grouped according to the purposes of the study. The first major group was subdivided into three groups (n = 6) including control, non-treated diabetic ...

    journal_title：European journal of drug metabolism and pharmacokinetics

    pub_type： 杂志文章

    doi：10.1007/s13318-013-0166-5

    authors： Malekinejad H,Rokhsartalab-Azar S,Hassani-Dizaj S,Alizadeh-Fanalou S,Rezabakhsh A,Amniattalab A

    更新日期：2014-12-01 00:00:00

  • Stereoselective disposition of RS-tocainide in man.

    abstract：:The disposition of RS-tocainide in three healthy volunteers has been studied after oral administration of a pseudoracemic mixture containing S(+) [3H] tocainide as a radioactive tracer together with a therapeutic dose of the racemate. Analytical methods based on HPLC have been developed to measure S(+) and R(-) tocain...

    journal_title：European journal of drug metabolism and pharmacokinetics

    pub_type： 杂志文章

    doi：10.1007/BF03189644

    authors： Hoffmann KJ,Renberg L,Bäärnhielm C

    更新日期：1984-07-01 00:00:00

  • Pharmacokinetics of pirazolac--a new anti-inflammatory drug--in human volunteers. I. Absorption, disposition, biotransformation and excretion.

    abstract：:The absorption, disposition, biotransformation and excretion of the nonsteroidal anti-inflammatory drug pirazolac were investigated in 6 volunteers (3 males, 3 females, age 50 greater than years) after intravenous and oral administration of 50 mg 14C-pirazolac as an aqueous solution of the sodium salt. Pirazolac was v...

    journal_title：European journal of drug metabolism and pharmacokinetics

    pub_type： 杂志文章

    doi：10.1007/BF03189696

    authors： Täuber U,Weiss C,Krause W,Acksteiner B,Matthes H

    更新日期：1985-01-01 00:00:00

  • Chlormezanone plasma and blood levels in patients after single and repeated oral doses and after suicidal drug overdose.

    abstract：:Chlormezanone plasma concentrations were determined in 5 volunteers (group 1) after a single oral dose of 200 mg of chlormezanone with high performance liquid chromatography. A plasma elimination half-life of 23 +/- 2.3 h was calculated. The mean peak chlormezanone plasma level was 1.86 +/- 0.2 micrograms/ml, 1 h afte...

    journal_title：European journal of drug metabolism and pharmacokinetics

    pub_type： 杂志文章

    doi：10.1007/BF03189873

    authors： Köppel C,Kristinsson J,Wagemann A,Tenczer J,Martens F

    更新日期：1991-01-01 00:00:00

  • A comparative "in vitro" study of permeability with different synthetic and biological membranes.

    abstract：:Permeability coefficients of seven compounds belonging to a true homologous series (4-alkylanilines) through several different synthetic and biological membranes were assayed in a two-chamber diffusion cell. Permeability-lipophilicity relationships for the experimental data were established and compared in order to as...

    journal_title：European journal of drug metabolism and pharmacokinetics

    pub_type： 杂志文章

    doi：

    authors： Díez-Sales O,Guzmán D,Cano D,Martín A,Sánchez E,Herráez M

    更新日期：1991-01-01 00:00:00

  • Interspecies similarities in the disposition of 3H-dihydroergotamine following subcutaneous administration in man and rabbits.

    abstract：:The disposition of dihydroergotamine methanesulfonate following single subcutaneous doses was studied in man and the rabbit using radiotracer techniques. 3H-Dihydroergotamine was almost immediately and completely absorbed from the injection site; peak blood radioactivity levels were attained within 1 h of drug adminis...

    journal_title：European journal of drug metabolism and pharmacokinetics

    pub_type： 杂志文章

    doi：10.1007/BF03189606

    authors： Tse FL,Jaffe JM

    更新日期：1984-01-01 00:00:00

  • Genetic Polymorphisms Affecting Cardiac Biomarker Concentrations in Children with Cancer: an Analysis from the "European Paediatric Oncology Off-patents Medicines Consortium" (EPOC) Trial.

    abstract：BACKGROUND AND OBJECTIVES:Doxorubicin plays an essential role in the treatment of paediatric cancers. Defining genotypes with a higher risk for developing anthracycline-induced cardiotoxicity could help to reduce cardiotoxicity. METHODS:Data originated from a phase II study assessing the pharmacokinetics of doxorubici...

    journal_title：European journal of drug metabolism and pharmacokinetics

    pub_type： 杂志文章

    doi：10.1007/s13318-019-00592-6

    authors： Hellmann F,Völler S,Krischke M,Jamieson D,André N,Bisogno G,Boddy A,Hempel G

    更新日期：2020-06-01 00:00:00

  • In vivo metabolism of 2-[1'-phenyl-3'-(3-chlorophenyl)-2'-propenylyden]hydrazino-3-methyl-4(3H)-quinazolinone in rats.

    abstract：:The aim of this study was to investigate by HPLC the in vivo metabolism of 2-[1'-phenyl-3'-(3-chlorophenyl)-2'-propenylyden]hydrazino-3-methyl-4(3H)-quinazolinone as a substrate, and as a model compound in rats. The substrate was dissolved in DMSO/water (1:4) and administered intraperitoneally at a dose of 100 mg/kg i...

    journal_title：European journal of drug metabolism and pharmacokinetics

    pub_type： 杂志文章

    doi：10.1007/BF03190629

    authors： Kaymakçioğlu BK,Aktan Y,Süzen S,Gökhan N,Koyunoğlu S,Erol K,Yeşilada A,Rollas S

    更新日期：2005-10-01 00:00:00

  • Pharmacokinetic Studies of Oxathio-Heterocycle Fused Chalcones.

    abstract：BACKGROUND AND OBJECTIVES:Chalcone constitutes one of the most used molecular frameworks in medicinal chemistry and its derivatives exhibit a broad spectrum of biological activities. Low absolute bioavailability, poor distribution, intensive metabolism and elimination of chalcones are the main problems in designing new...

    journal_title：European journal of drug metabolism and pharmacokinetics

    pub_type： 杂志文章

    doi：10.1007/s13318-016-0320-y

    authors： Okoniewska K,Konieczny MT,Lemke K,Grabowski T

    更新日期：2017-02-01 00:00:00

  • Stable isotope methodology for studying the performance of metoprolol Oros tablets in comparison to conventional and slow release formulations.

    abstract：:Metoprolol Oros tablets were designed to deliver their drug content as a constant rate over a period of time longer than that currently recorded with slow-release dosage forms. The bioavailability of 7/95, 14/190 and 21/285 Oros tablets was compared to that of either 100 mg conventional or 200 mg slow-release Lopresor...

    journal_title：European journal of drug metabolism and pharmacokinetics

    pub_type： 杂志文章

    doi：10.1007/BF03188865

    authors： Richard J,Cardot JM,Godbillon J

    更新日期：1994-10-01 00:00:00

  • Characterizing the Effects of Race/Ethnicity on Acetaminophen Pharmacokinetics Using Physiologically Based Pharmacokinetic Modeling.

    abstract：BACKGROUND AND OBJECTIVES:Acetaminophen (APAP, paracetamol) is currently the principal cause of acute liver failure in both the USA and the UK. However, relatively little is known about the influence of genes and race/ethnicity on the disposition of APAP and the extent to which genetic variation and ethnicity may predi...

    journal_title：European journal of drug metabolism and pharmacokinetics

    pub_type： 杂志文章

    doi：10.1007/s13318-016-0329-2

    authors： Zurlinden TJ,Reisfeld B

    更新日期：2017-02-01 00:00:00

  • Parameterization of Microsomal and Cytosolic Scaling Factors: Methodological and Biological Considerations for Scalar Derivation and Validation.

    abstract：:Mathematical models that can predict the kinetics of compounds have been increasingly adopted for drug development and risk assessment. Data for these models may be generated from in vitro experimental systems containing enzymes contributing to metabolic clearance, such as subcellular tissue fractions including micros...

    journal_title：European journal of drug metabolism and pharmacokinetics

    pub_type： 杂志文章

    doi：10.1007/s13318-020-00666-w

    authors： Doerksen MJ,Jones RS,Coughtrie MWH,Collier AC

    更新日期：2020-12-19 00:00:00

  • Apomorphine pharmacokinetics in parkinsonism after intranasal and subcutaneous application.

    abstract：:Apomorphine was administered subcutaneously and intranasally to 7 patients suffering from Parkinsonism with 'on-off' problems. This comparative pharmacokinetic study showed that the two routes of administration are comparable with respect to absorption kinetics. Apomorphine is rapidly absorbed when administered intran...

    journal_title：European journal of drug metabolism and pharmacokinetics

    pub_type： 临床试验,杂志文章

    doi：10.1007/BF03192285

    authors： Sam E,Jeanjean AP,Maloteaux JM,Verbeke N

    更新日期：1995-01-01 00:00:00

  • One-compartmental biometric blood loss calculation after cesarean section.

    abstract：:Blood loss during cesarean section was calculated based on post-operative decrement of hemoglobin (Hb) and hematocrit (Hct) level. The model used for pregnant women was previously validated for non-pregnant women who underwent gynecological surgery. 1,068 pregnant women who underwent cesarean section and 517 women who...

    journal_title：European journal of drug metabolism and pharmacokinetics

    pub_type： 杂志文章

    doi：10.1007/s13318-011-0042-0

    authors： Milosevic N,Popovic J,Grujic Z,Rapaic M

    更新日期：2011-09-01 00:00:00

  • Pharmacokinetics of Panax notoginseng Saponins in Adhesive and Normal Preparation of Fufang Danshen.

    abstract：BACKGROUND AND OBJECTIVE:Fufang Danshen formula, a famous Chinese patent medicine containing Salvia miltiorrhiza, Panax notoginseng and borneol, has been widely used in the treatment of coronary heart disease. The application is restricted by low bioavailability partly due to Panax notoginseng saponins (PNS) instabilit...

    journal_title：European journal of drug metabolism and pharmacokinetics

    pub_type： 杂志文章

    doi：10.1007/s13318-017-0433-y

    authors： Chen XN,Li DQ,Zhao MD,Yu GY,Du SY,Lu Y,Bai J,Li PY,Wu YL,Tian ZH,Zeng YY

    更新日期：2018-04-01 00:00:00

  • Pharmacokinetic and pharmacodynamic aspects of concomitant mibefradil-digoxin therapy at therapeutic doses.

    abstract：:This study investigated the effect of mibefradil on digoxin pharmacokinetics an pharmacodynamics. Following a loading dose of digoxin (0.375 mg, three times, day 1), 0.375 mg was administered once daily to 40 healthy subjects (days 2-15). Mibefradil was administered daily at 50 mg, 100 mg, or 150 mg (days 9-15). With ...

    journal_title：European journal of drug metabolism and pharmacokinetics

    pub_type： 临床试验,杂志文章

    doi：10.1007/BF03190358

    authors： Peters J,Welker HA,Bullingham R

    更新日期：1999-04-01 00:00:00

  • 4-Amino-3-(3'-methoxycarbonyl-2'-thioureido)benzophenone, a prodrug of mebendazole.

    abstract：:The compound 4-amino-3-(3'-methoxycarbonyl-2'-thioureido) benzophenone has shown promise as a prodrug of the anthelmintic mebendazole. The compound is stable in acid and neutral media and is rapidly hydrolysed in base. An HPLC assay procedure for mebendazole, the prodrug and their known or expected metabolites and deg...

    journal_title：European journal of drug metabolism and pharmacokinetics

    pub_type： 杂志文章

    doi：10.1007/BF03188765

    authors： Dawson M,Watson TR

    更新日期：1983-10-01 00:00:00

  • Deuterium isotope effects on caffeine metabolism.

    abstract：:The aim of this work was to study the influence of labelling on caffeine metabolism according to the incubation mode. It has been observed that labelling induces an isotopic effect on metabolisation speed: apparent half-lives are systematically increased. Moreover, isotopic effects are in agreement with those previous...

    journal_title：European journal of drug metabolism and pharmacokinetics

    pub_type： 杂志文章

    doi：10.1007/BF03189795

    authors： Benchekroun Y,Dautraix S,Desage M,Brazier JL

    更新日期：1997-04-01 00:00:00

  • Disposition of epirubicin in an oily contrast medium after intravenous and intrahepato-arterial administration in liver cancer: a preliminary report.

    abstract：:The present study reports findings on the disposition of epirubicin after an intrahepato-arterial administration of the Lipiodol-drug complex, prepared by mixing the drug-aqueous phase with the iodized oil by ultra-sonification, in 14 patients with histologically proven hepatoma or hepatomegaly with serum alpha-fetopr...

    journal_title：European journal of drug metabolism and pharmacokinetics

    pub_type： 杂志文章

    doi：10.1007/BF03190149

    authors： Lee K,Chan K,Leung WT,Leung NW,Ho S,Chan M,Lau CC,Tao M,Lau WY,Shiu W

    更新日期：1992-07-01 00:00:00

  • Effect of induced hypoalbuminemia on distribution, total clearance and unbound clearance of piroxicam in vivo in the rat.

    abstract：:The influence of decreased albumin concentration on the pharmacokinetic behaviour of Piroxicam was studied in vivo in rats that had undergone plasmapheresis. Reductions of approximately 25% and 50% in the plasma albumin concentration were achieved, the former in rats not given plasma expander, the latter in animals gi...

    journal_title：European journal of drug metabolism and pharmacokinetics

    pub_type： 杂志文章

    doi：10.1007/BF03188792

    authors： Troconiz JI,Lopez-Bustamante LG,Fos D

    更新日期：1993-04-01 00:00:00

  • The effect of food and antacids on lansoprazole absorption and disposition.

    abstract：:Bioavailability of lansoprazole, a new gastric proton pump inhibitor, was investigated in 12 healthy subjects. Each subject received in random order, lansoprazole (30 mg) alone or associated with standard meal or with antacids (aluminium and magnesium hydroxides) or one hour later than antacids. Lansoprazole and metab...

    journal_title：European journal of drug metabolism and pharmacokinetics

    pub_type： 临床试验,杂志文章,随机对照试验

    doi：

    authors： Delhotal-Landes B,Cournot A,Vermerie N,Dellatolas F,Benoit M,Flouvat B

    更新日期：1991-01-01 00:00:00

  • Absolute bioavailability study in the dog with Visacor, a new cardioselective beta blocking drug with intrinsic sympathomimetic activity.

    abstract：:The cardioselective beta-adrenergic blocking drug Visacor (ICI 141,292) was dosed to six beagle dogs in a randomized cross-over manner. Five formulations were examined i.e. a 15 mg/kg intravenous solution, a 50 mg/kg oral solution, and 50, 100 and 200 mg/kg oral powder formulations. Whole blood and urine samples were ...

    journal_title：European journal of drug metabolism and pharmacokinetics

    pub_type： 杂志文章

    doi：10.1007/BF03189616

    authors： McAinsh J,Smith RP,Ferguson RA

    更新日期：1984-04-01 00:00:00

  • Differences in Intestinal Metabolism of Ginseng Between Normal and Immunosuppressed Rats.

    abstract：BACKGROUND AND OBJECTIVE:Ginseng is usually consumed as a dietary supplement for health care in the normal state or prescribed as a herbal medicine in pathologic conditions. Although metabolic studies of ginseng are commonly performed on healthy organisms, the metabolic characteristics in pathologic organisms remain un...

    journal_title：European journal of drug metabolism and pharmacokinetics

    pub_type： 杂志文章

    doi：10.1007/s13318-020-00645-1

    authors： Zhu JH,Xu JD,Zhou SS,Zhang XY,Zhou J,Kong M,Mao Q,Zhu H,Li SL

    更新日期：2021-01-01 00:00:00

  • Stereoselective Pharmacokinetics of Ketoprofen After Oral Administration of Modified-Release Formulations in Caucasian Healthy Subjects.

    abstract：BACKGROUND AND OBJECTIVES:Ketoprofen, a potent nonsteroidal anti-inflammatory drug, is clinically administered as a racemic mixture. One of the possible metabolism routes of ketoprofen is the inversion of the R- to S-enantiomer in the gastrointestinal tract. Ketoprofen, as a weak acid drug, might undergo recirculation ...

    journal_title：European journal of drug metabolism and pharmacokinetics

    pub_type： 临床试验,杂志文章,随机对照试验

    doi：10.1007/s13318-015-0313-2

    authors： Lorier M,Magallanes L,Ibarra M,Guevara N,Vázquez M,Fagiolino P

    更新日期：2016-12-01 00:00:00

  • Molecular profiling of non-genotoxic hepatocarcinogenesis using differential display reverse transcription-polymerase chain reaction (ddRT-PCR).

    abstract：:The technique of differential display reverse transcription-polymerase chain reaction (ddRT-PCR) has been used to produce unique profiles of up-regulated and down-regulated gene expression in the liver of male Wistar rats following short term exposure to the non-genotoxic hepatocarcinogens, phenobarbital and WY-14,643...

    journal_title：European journal of drug metabolism and pharmacokinetics

    pub_type： 杂志文章

    doi：10.1007/BF03190966

    authors： Rockett JC,Esdaile DJ,Gibson GG

    更新日期：1997-10-01 00:00:00

  • Isolation and characterization of the urinary metabolites of arbaprostil in the male dog after intravenous administration.

    abstract：:The profile of urinary metabolites of 3H-arbaprostil was characterized in the male dog after intravenous administration. The major metabolites were purified and their structures deduced by gas chromatography/mass spectrometry (GC/MS) studies after conversion to the methyl ester-methoxime-trimethylsilyl ether derivativ...

    journal_title：European journal of drug metabolism and pharmacokinetics

    pub_type： 杂志文章

    doi：10.1007/BF03191312

    authors： Thornburgh BA,Shaw SR,Bronson GE,Sinha AJ

    更新日期：1988-04-01 00:00:00

  • Pharmacokinetic and pharmacodynamic data and models in clinical trials.

    abstract：:There is current emphasis for extended integration of pharmacokinetics (PK) and pharmacodynamics (PD) into all phases of new drug development, including large-scale clinical trials. In this paper, we focus on study design and data analysis issues for the investigation of pharmacokinetic/pharmacodynamic and blood level...

    journal_title：European journal of drug metabolism and pharmacokinetics

    pub_type： 杂志文章,评审

    doi：10.1007/BF03220009

    authors： Steimer JL,Ebelin ME,Van Bree J

    更新日期：1993-01-01 00:00:00

  • Effect of stevioside and sodium salt of monoketocholic acid on glycemia in normoglycemic and diabetic rats.

    abstract：:This study investigated the effect of a commercial preparation of stevioside and a synthetic compound, sodium salt of monketocholic acid (MKC), administered per os (p.o.) and also adminstered via an osmotic pump, on glycemia in normoglycemic and diabetic Wistar rats. Diabetes was induced with alloxan, 100 mg/kg, i.p. ...

    journal_title：European journal of drug metabolism and pharmacokinetics

    pub_type： 杂志文章

    doi：10.1007/BF03191014

    authors： Rasković A,Mikov M,Skrbić R,Jakovljević V,Vasović V,Posa M,Kuhajda K,Kevresan S,Tomic Z,Siladji D

    更新日期：2008-01-01 00:00:00